Fe(II)/α-Ketoglutarate-Dependent Hydroxylases and Related Enzymes

REFERENCES

• Aas, P.A., Otterlei, M., Falnes, P.O., Vagbe, C.B., Skorpen, F., Akbari, M., Sundheim, O., Bjoras, M., Slupphaug, G., Seeberg, E., and Krokan, H.E. 2003. Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA. Nature 421:859- 863.
   Google Scholar
• Abbott, M.T., Schandl, E.K., Lee, R.F., Parker, T.S., and Midgett, RJ. 1967. Cofactor requirements of thymine hydroxylase. Biochim Bio-phys Acta 132:525-528.
   Google Scholar
• Abbott, M.T. and Udenfriend, S. 1974. a-Ketoglutarate-coupled dioxy-genases, In: Molecular Mechanisms of Oxygen Activation. pp. 167- 214, O. Hayaishi, Ed., Academic Press, New York.
   Google Scholar
• Abbruzzese, A., Hanauske-Able, H.M., Park, M.H., Henke, S., and Folk, J.E. 1991. The active site of deoxyhypusyl hydroxylase: useof catecholpeptides and their component chelator and peptide moieties as molecular probes. Biochim Biophys Acta 1077:159-166.
   Google Scholar
• Abbruzzese, A., Park, M.H., and Folk, J.E. 1986. Deoxyhypusine hy-droxylase from rat testis. Partial purification and characterization. J Biol Chem 261:3085-3089.
   Google Scholar
• Adams, D.O. and Yang, S.F. 1979. Ethylenebiosynthesis: identification of 1-aminopropane-1-carboxylic acid as an intermediate in the conversion of methionine to ethylene. Proc Natl Acad Sci USA 76:170-174.
   Google Scholar
• Annunem, P., Koivunen, P., and Kivirikko, K.I. 1999. Cloning of the a-subunit of prolyl 4-hydroxylase from Drosophila and expression and characterization of the corresponding enzyme tetramer with some unique properties. J Biol Chem 274:6790-6796.
   Google Scholar
• Anzellotti, D. and Ibrahim, R.K. 2000. Novel flavonol 2-oxoglutarate dependent dioxygenase: affinity purification, characterization, and kinetic properties. Arch Biochem Biophys 382:161-172.
   Google Scholar
• Aravind, L. and Koonin, E.V. 2001. The DNA-repair protein AlkB, EGL-9, and leprecan define new families of 2-oxoglutarate-dependent- and iron-dependent dioxygenases. Genomebiology.com 2:7.1-7.8.
   Google Scholar
• Baker, B.J., Dotzlaf, J.E., and Yeh, W.-K. 1991. Deacetoxy-cephalosporin C hydroxylase of Streptomyces clavuligerus. Purification, characterization, bifunctionality, and evolutionary implication. J Biol Chem 266:5087-5093.
   Google Scholar
• Baldwin, J.E. and Abraham, E. 1988. The biosynthesis of penicillins and cephalosporins. Nat ProdRep 5:129-145.
   Google Scholar
• Baldwin, J.E., Adlington, R.M., Coates, J.B., Crabbe, M.J.C., Crouch, N.P, Keeping, J.W., Knight, G.C., Schofield, C.J., Ting, H.-H., Vallejo, C.A., Thorniley, M., and Abraham, E.P 1987. Purification and initial characterization of an enzyme with deacetoxy-cephalosporin C synthetase and hydroxylase activities. Biochem J 245:831-841.
   Google Scholar
• Baldwin, J.E., Adlington, R.M., Crouch, N.P, andPereira, I.A.C. 1993. Incorporation of 18O-labelled water into oxygenated products pro-duced by the enzyme deacetoxy/deacetylcephalosporin C synthase. Tetrahedron 49:7499-7518.
   Google Scholar
• Baldwin, J.E., Adlington, R.M., Schofield, C.J., Sobey, W.J., andWood, M.E. 1989. The role of a-ketoglutarate in cephalosporin biosynthesis. Chem Commun 1012-1015.
   Google Scholar
• Bankel, L., Lindstedt, G., and Lindstedt, S. 1972. Thymidine 2'-hydroxylation in Neurospora crassa. J Biol Chem 247:6128-6134.
   Google Scholar
• Barlow, J.N., Zhang, Z., John, P., Baldwin, J.E., and Schofield, C.J. 1997. Inactivation of 1-aminocyclopropane-1-carboxylate oxidase involves oxidative modification. Biochemistry 36:3563-3569.
   Google Scholar
• Bohm, B.A. 1998. Introduction to Flavonoids. Harwood Academic Publishers, Amsterdam, The Netherlands.
   Google Scholar
• Borovok, I., Landman, O., Kreisberg-Zakarin, R., Aharonowitz, Y, and Cohen, G. 1996. Ferrous active site of isopenicillin N synthase: genetic and sequence analysis of the endogenous ligands. Biochemistry 35:1981-1987.
   Google Scholar
• Bradley, F.C., Lindstedt, S., Lipscomb, J.D., Que, L., Jr., Roe, A.L., and Rundgren, M. 1986. 4-Hydroxyphenylpyruvate dioxygenase is an iron-tyrosinate protein. J Biol Chem 261:11693-11696.
   Google Scholar
• Britsch, L. 1990. Purification and characterization of flavone synthase I, a 2-oxoglutarate-dependent desaturase. Arch Biochem Biophys 282:152-160.
   Google Scholar
• Britsch, L., Dedio, J., Saedler, H., and Forkmann, G. 1993. Molecular characterization of flavanone 3ß-hydroxylases. Consensus sequence, comparison with related enzymes and the role of conserved histidine residues. Eur J Biochem 217:745-754.
   Google Scholar
• Britsch, L. and Grisebach, H. 1986. Purification and characterization of (2S)-flavanone 3-hydroxylase from Petunia hybrida. Eur J Biochem 156:569-577.
   Google Scholar
• Britsch, L., Ruhnau-Brich, B., and Forkmann, G. 1992. Molecular cloning, sequence analysis, and in vitro expression of flavanone 3/3-hydroxylase from Petunia hybrida. J Biol Chem 267:5380-5387.
   Google Scholar
• Bruick, R.K. and McKnight, S.L. 2001. A conserved family of prolyl-4-hydroxylases that modify HIF. Science 294:1337-1340.
   Google Scholar
• Brunhuber, N.M.W., Mort, J.L., Christoffersen, R.E., and Reich, N.O. 2000. Steady-state kinetic mechanism of recombinant avocado ACC oxidase: initial velocity and inhibitor studies. Biochemistry 39:10730-10738.
   Google Scholar
• Burzlaff, N.I., Rutledge, P.J., Clifton, I.J., Hensgens, C.M.H., Pickford, M., Adlington, R.M., Roach, PL., and Baldwin, J.E. 1999. The reaction cycle of isopenicillin N synthase observed by X-ray diffraction. Nature 401:721-724.
   Google Scholar
• Busby, R.W., Chang, M.D.-T., Busby, R.C., Wimp, J., and Townsend, C.A. 1995. Expression and purification of two isozymes of clavam-inate synthase and initial characterization of the iron binding site. General error analysis in polymerase chain reaction amplification. J Biol Chem 270:4262-4269.
   Google Scholar
• Calcutt, M.J. and Schmidt, FJ. 1994. Gene organization in the bleomycin-resistance region of the producer organism. Streptomycin verticillus. Gene 151:17-21.
   Google Scholar
• Chahal, A., Khan, M., Pai, S.G., Barbosa, E., and Singh, I. 1998. Restoration of phytanic acid oxidation in Refsum disease fibrob-lasts from patients with mutations in the phytanoyl-CoA hydroxylase gene. FEBS Lett 429:119-122.
   Google Scholar
• Chance, M.R., Bresnick, A.R., Burley, S.K., Jiang, J.-S., Lima, CD., Sali, A., Almo, S.C., Bonanno, J.B., Buglino, J.A., Boulton, S., Chen, H., Eswar, N., He, G., Huang, R., Iiyin, V., McMahan, L., Pieper, U., Ray, S., Vidal, M., and Wang, L.K. 2002. Structural genomics: a pipeline for providing structures for the biochemist. Prot Science 11:723-738.
   Google Scholar
• Charrier, B., Coronado, C, Kondorosi, A., and Ratet, P. 1995. Molec-ular characterization and expression of alfalfa (Medicago sativa L.) flavanone 3-hydroxylase and dihydroflavonol-4-reductase encoding genes. Plant Molec Biol 29:773-786.
   Google Scholar
• Chen, B.J., Carroll, P., and Samson, L. 1994. The Escherichia coli AlkB protein protects human cells against alkylation-induced toxicity. J Bacteriol 176:6255-6261.
   Google Scholar
• Chen, H., Thomas, M.G., O'Conner, S.E., Hubbard, B.K., Burkart, M.D., and Walsh, C.T. 2001. Aminoacyl-S-enzyme intermediates in /3-hydroxylations and a,/3-desaturations of amino acids in peptide antibiotics. Biochemistry 40:1651-11659.
   Google Scholar
• Chen, K. and Que, L., Jr. 1999. Evidence for the participation of a high-valent iron-oxo species in stereospecific alkane hydroxylation by a non-heme iron catalyst. Chem Commun 1375-1376.
   Google Scholar
• Chen, V.J., Orville, A.M., Harpel, M.R., Frolik, C.A., Surerus, K.K., Munck, E., and Lipscomb, J.D. 1989. Spectroscopic studies of isopenicillin N synthase. A mononuclear nonheme Fe2+ oxidase with metal coordination sites for small molecules and substrate. J Biol Chem 264:21677-21681.
   Google Scholar
• Chen, W., Zeng, H., and Tan, H. 2000. Cloning, sequencing, and function of sanF: a gene involved in nikkomycin biosythesis of Strepto-myces ansochromogenes. Curr Microbiol 41:312-316.
   Google Scholar
• Chiang, H.H., Hwang, I., and Goodman, H.M. 1995. Isolation of the Arabidopsis GA4 locus. Plant Cell 7:195-201.
   Google Scholar
• Choroba, O.W., Williams, D.H., and Spencer, J.B. 2000. Biosynthesis of the vancomycin group of antibiotics: involvement of an unusual dioxygenase in the pathway to (S)-4-hydroxyphenylglycine. J Am Chem Soc 122:5389-5390.
   Google Scholar
• Clement, P.M., Hanauske-Abel, H.M., Wolff, E.C., Kleinman, H.K., and Park, M.H. 2002. The antifungal drug ciclopirox inhibits de-oxyhypusine and proline hydroxylation, endothelial cell growth and angiogenesis in vitro. Int J Cancer 100:491-498.
   Google Scholar
• Clifton, I.J., Doan, L.X., Sleeman, M.C., Topf, M., Suzuki, H., Wilmouth, R.C., and Schofield, C.J. 2003. Crystal structure of car-bapenem synthase (CarC). J Biol Chem 278:20843-20850.
   Google Scholar
• Clifton, I.J., Hsueh, L.-C, Baldwin, J.E., Harlos, K., and Schofield, C.J. 2001. Structure of proline 3-hydroxylase. Evolution of the family of 2-oxoglutarate dependent dioxygenases. Eur J Biochem 268:6625-6636.
   Google Scholar
• Cosper, N.J., Stalhandske, C.M.V., Saari, R.E., Hausinger, R.P, and Scott, R.A. 1999. X-ray absorption spectroscopic analysis of Fe(II) and Cu(II) forms of an herbicide-degrading a-ketoglutarate dioxy-genase. J Biol Inorg Chem 4:122-129.
   Google Scholar
• Counts, D.F., Cardinale, G.J., and Udenfriend, S. 1978. Prolyl hydroxylase half reaction: peptidyl prolyl-independent decarboxylation of a-ketoglutarate. Proc Natl AcadSci USA 75:2145-2149.
   Google Scholar
• Croes, K., Casteels, M., Asselberghs, S., Herdewijn, P., Mannaerts, G.P, and Van Veldhoven, P.P. 1997a. Formation of 2-methyl-branched fatty aldehyde during peroxisomal a-oxidation. FEBS Lett 412:643-645.
   Google Scholar
• Croes, K., Van Veldhoven, P.P., Mannaerts, G.P, and Casteels, M. 1997b. Production of formyl-CoA during peroxisomal a-oxidation of 3-methyl-branched fatty acids. FEBS Lett 407:197-200.
   Google Scholar
• Croes, K., Foulon, V, Casteels, M., Van Veldhoven, P.P., and Mannaerts, G.P. 2000. Phytanoyl-CoA hydroxylase: recognition of 3-methyl-branched acyl-CoAs and requirement for GTP or ATP and Mg2+ in addition to its known hydroxylation cofactors. J Lipid Res 41:629-636.
   Google Scholar
• Crouch, N.P, Adlington, R.M., Baldwin, J.E., Lee, M.-H., and MacKinnon, C.H. 1997. A mechanistic rationalization for the substrate specificity of recombinant mammalian 4-hydroxyphenyl-pyruvate dioxygenase (HPPD). Tetrahedron 53:6993-7010.
   Google Scholar
• Cundliffe, E., Bate, N., Butler, A., Fish, S., Gandecha, A., and Merson-Davies, L. 2001. The tylosin-biosynthetic genes of Streptomycesfra-diae. Antonie van Leeuwenhoek 79:229-234.
   Google Scholar
• Dames, S.A., Martinez-Yamout, M., De Guzman, R.N., Dyson, H.J., and Wright, PE. 2002. Structural basis for HIF-1a/CBP recognition in the cellular hypoxic response. Proc Natl Acad Sci USA 99:5271-5276.
   Google Scholar
• Dann, CE., Bruick, R.K., and Deisenhofer, J. 2002. Structure of a factor-inhibiting hypoxia-inducible factor 1: an essential asparaginyl hydroxylase involved in the hypoxic response pathway. Proc Natl AcadSci USA 99:15351-15356.
   Google Scholar
• Carolis, E., Chan, F., Balsevich, J., and De Luca, V. 1990. Isola-tion and characterization of a 2-oxoglutarate dependent dioxygenase involved in the second-to-last step in vindoline biosynthesis. Plant Physiol 94:1323-1329.
   Google Scholar
• Carolis, E. and De Luca, V. 1993. Purification, characterization, and kinetic analysis of a 2-oxoglutarate-dependent dioxygenase involved in vindoline biosynthesis from Catharanthus roseus. J Biol Chem 268:5504-5511.
   Google Scholar
• Carolis, E. and De Luca, V. 1994. 2-Oxoglutarate-dependent dioxy-genases and related enzymes: biochemical characterization. Phy-tochem 36:1093-1107.
   Google Scholar
• Dinglay, S., Trewick, S.C., Lindahl, T., and Sedgwick, B. 2000. Defec-tive processing of methylated single-stranded DNA by E. coli alkB mutants. Genes Develop 14:2097-2105.
   Google Scholar
• Dong, J.G., Fernandez-Maculet, J.C., and Yang, S.F. 1992. Purifica-tion and characterization of 1-aminoacyclopropane-1-carboxylate oxidase from apple fruit. Proc Natl Acad Sci USA 89:9789-9793.
   Google Scholar
• Dotzlaf, J.E. and Yeh, W.-K. 1987. Copurification and characteri-zation of deacetoxycephalosporin C synthetase/hydroxylase from Cephalosporium acremonium. J Bacteriol 169:1611-1618.
   Google Scholar
• Dotzlaf, J.E. and Yeh, W.-K. 1989. Purification and properties of deace-toxycephalosporin C synthase from recombinant Escherichia coli and its comparison to the native enzyme purified from Streptomyces clavuligerus. J Biol Chem 264:10219-10227.
   Google Scholar
• Duncan, T., Trewick, S.C., Koivisto, P., Bates, P.A., Lindahl, T., and Sedgwick, B. 2002. Reversal of DNA alkylation damage by two human dioxygenases. Proc Natl Acad Sci USA 99:16660- 16665.
   Google Scholar
• Dunning Hotopp, J.C., Auchtung, T.A., Hogan, D.A., and Hausinger, R.P. 2003. Intrinsic tryptophan fluorescence as a probe of metal and ketoglutarate binding to TfdA, a mononuclear non-heme iron dioxygenase. J Inorg Biochem 93:66-70.
   Google Scholar
• Dunning Hotopp, J.C. and Hausinger, R.P. 2001. Alternative sub-strates for 2,4-dichlorophenoxyacetate/-ketoglutarate dioxygenase. J Molec Catalysis B 15:155-162.
   Google Scholar
• Dunning Hotopp, J.C. and Hausinger, R.P. 2002. Probing the 2,4-dichlorophenoxyacetate/-ketoglutarate dioxygenase substrate binding site by site-directed mutagenesis and mechanism-based in-activation. Biochemistry 41:9787-9794.
   Google Scholar
• Eichhorn, E., van der Ploeg, J.R., Kertesz, M.A., and Leisinger, T. 1997. Characterization of -ketoglutarate-dependent taurine dioxygenase from Escherichia coli. J Biol Chem 272:23031-23036.
   Google Scholar
• Elkins, J.M., Hewitson, K.S., McNeill, L.A., Seibel, J.F., Schlemminger, I., Pugh, C.W., Ratcliffe, P.J., and Schofield, C.J. 2003. Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1. J Biol Chem 278:1802-1806.
   Google Scholar
• Elkins, J.M., Ryle, M.J., Clifton, I.J., Dunning Hotopp, J.C., Lloyd, J.S., Burzlaff, N.I., Baldwin, J.E., Hausinger, R.P., and Roach, P.L. 2002. X-ray crystal structure of Escherichia coli taurine/-ketoglutarate dioxygenase complexed to ferrous iron and substrates. Biochemistry 41:5185-5192.
   Google Scholar
• Epstein, A.C.R., Gleadle, J.M., McNeill, L.A., Hewitson, K.S., O'Rourke, J., Mole, D.R., Mukherji, M., Metzen, E., Wilson, M.I., Dhanda, A., Tian, Y.-M., Masson, N., Hamilton, D.L., Jaakkola, P., Barstead, R., Hodgkin, J., Maxwell, P.H., Pugh, C.W., Schofield, C.J., and Ratcliffe, P.J. 2001. C. elegans EGL-9 and mammalian ho-mologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 107:43-54.
   Google Scholar
• Ericksson, M., Myllyharju, J., Tu, H., Hellman, M., and Kivirikko, K.I. 1999. Evidence for 4-hydroxyproline in viral proteins. Characteriza-tion of a viral prolyl 4-hydroxylase and its peptide substrates. J Biol Chem 274:22131-22134.
   Google Scholar
• Falnes, P.O., Johansen, R.F., and Seeberg, E. 2002. AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli. Nature 419:178-182.
   Google Scholar
• Foulon, V., Antonenkov, V.D., Croes, K., Waelkens, E., Mannaerts, G.P., Van Veldhoven, P.P., and Casteels, M. 1999. Purification, molecular cloning, and expression of 2-hydroxyphytanoyl-CoA lyase, a perox-isomal thiamin pyrophosphate-dependent enzyme that catalyzes the carbon-carbon cleavage during -oxidation of 3-methyl-branched fatty acids. Proc Natl Acad Sci USA 96:10039-10044.
   Google Scholar
• Freedman, S.J., Sun, Z.-Y.J., Poy, F., Kung, A.L., Livingston, D.M., Wagner, G., and Eck, M.J. 2002. Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1. Proc Natl Acad Sci USA 99:5367-5372.
   Google Scholar
• Frey, M., Huber, K., Park, W.J., Sicker, D., Lindberg, P., Meeley, R.B., Simmons, C.R., Yalpani, N., and Gierl, A. 2003. A 2-oxoglutarate-dependent dioxygenase is integrated in the DIMBOA-biosynthesis. Phytochem 62:371-376.
   Google Scholar
• Fukuda, H., Fujii, T., and Ogawa, T. 1986. Preparation of a cell-free ethylene-forming system from Penicillium digitatum. Agric Biol Chem 50:977-981.
   Google Scholar
• Fukuda, H., Kitajima, H., Fujii, T., Tazaki, M., and Ogawa, T. 1989. Purification and some properties of a novel ethylene-forming enzyme produced by Penicillium digitatum. FEMS Microbiol Lett 59:1-6.
   Google Scholar
• Fukuda, H., Ogawa, T., Ishihara, K., Fujii, T., Nagahama, K., Omata, T., Inoue, Y., Tanase, S., and Morino, Y. 1992a. Molecular cloning in Escherichia coli, expression, and nucleotide sequence of the gene for the ethylene-forming enzyme of Pseudomonas syringae pv. phase-olicola PK2. Biochem Biophys Res Commun 188:826-832.
   Google Scholar
• Fukuda, H., Ogawa, T., Tazaki, M., Nagahama, K., Fujii, T., Tanase, S., and Morino, Y. 1992b. Two reactions are simultaneously catalyzed by a single enzyme: the arginine-dependent simultaneous formation of two products, ethylene and succinate, from 2-oxoglutarate by an enzyme from Pseudomonas syringae. Biochem Biophys Res Commun 188:483-489.
   Google Scholar
• Fukumori, F. and Hausinger, R.P. 1993a. Purification and characteri-zation of 2,4-dichlorophenoxyacetate/-ketoglutarate dioxygenase. J Biol Chem 268:24311-24317.
   Google Scholar
• Fukumori, F. and Hausinger, R.P. 1993b. Alcaligenes eutrophus JMP134 "2,4-dichlorophenoxyacetate monooxygenase" is an -ketoglutarate-dependent dioxygenase. J Bacteriol 175:2083-2086.
   Google Scholar
• Galland, S., Le Borgne, F., Bouchard, F., Georges, B., Clouet, P., Grand-Jean, F., and Demarquoy, J. 1999. Molecular cloning and characterization of the cDNA encoding rat liver butyrobetaine hy-droxylase. Biochim Biophys Acta 1441:85-92.
   Google Scholar
• Garcia Costas, A.M., White, A.K., and Metcalf, W.W. 2001. Purifica-tion and characterization of a novel phosphorus-oxidizing enzyme from Pseudomonas stutzeri WM88. J Biol Chem 276:17429-17436.
   Google Scholar
• Gibbons, H.S., Lin, S., Cotter, R.J., and Raetz, C.R.H. 2000. Oxy-gen requirement for the biosynthesis of the S-2-hydroxymyristate moiety in Salmonella typhimurium lipid A. Function of LpxO, a newFe2+/-ketoglutarate-dependentdioxygenasehomologue.JBiol Chem 275:32940-32949.
   Google Scholar
• Goto, M. and Hyodo, H. 1987. Ethylene production by cell-free extract of the kudzu strain of Pseudomonas syringae pv. phaseolicola. Plant Cell Physiol 28:405-414.
   Google Scholar
• Gronke, R.S., VanDusen, W.J., Garsky, V.M., Jacobs, J.W., Sardana, M.K., Stern, A.M., and Friedman, P.A. 1989. Aspartyl fi-hydroxylase: in vitro hydroxylation of a synthetic peptide based on the structure of the first growth factor-like domain of human factor IX. Proc Natl Acad Sci USA 86:3609-3613.
   Google Scholar
• Gunsior, M., Ravel, J., Challis, G.L., and Townsend, C.A. 2004. Engineering p -hydroxyphenylpyruvate dioxygenase to a p-hydroxymandelate synthase and evidence for the proposed benzene oxide intermediate in homogentisate formation. Biochemistry 43:663-674.
   Google Scholar
• Haefele, C, Bonfils, C, and Sauvaire, Y. 1997. Characterization of a dioxygenase from Trigonella foenum-graecum involved in 4-hydroxyisoleucine biosythesis. Phytochem 44:563-566.
   Google Scholar
• Hamilton, A.J., Bouzayen, M., and Grierson, D. 1991. Identification of a tomato gene for the ethylene-forming enzyme by expression in yeast. Proc Natl Acad Sci USA 88:7434-7437.
   Google Scholar
• Han, H. and Pascal, R.A., Jr. 1990. a-Ketoisocaproate dioxygenase: the stereochemical course of the hydroxylation reaction. J Org Chem 55:5173-5176.
   Google Scholar
• Han, S., Eltis, L.D., Timmis, K.N., Muchmore, S.W., and Bolin, J.T. 1995. Crystal structure of the biphenyl-cleaving extradiol dioxyge-nase from a PCB-degrading pseudomonad. Science 270:976-980.
   Google Scholar
• Hanauske-Abel, H.M. and Gunzler, V. 1982. A stereochemical concept for the catalytic mechanism of prolylhydroxylase. Applicability to classification and design of inhibitors. J Theor Biol 94:421-455.
   Google Scholar
• Hashimoto, T., Matsuda, J., and Yamada, Y. 1993. Two-step epoxi-dation of hyoscyamine to scopolamine is catalyzed by bifunctional hyoscyamine 6ß-hydroxylase. FEBS Lett 329:35-39.
   Google Scholar
• Hashimoto, T. and Yamada, Y. 1987. Purification and characterization of hyoscyamine 6/3-hydroxylase from root cultures of Hyoscyamus niger L. Hydroxylase and epoxidase activities of enzyme preparations. Eur JBiochem 164:277-285.
   Google Scholar
• Hausinger, R.P, Fukumori, F., Hogan, D.A., Sassanella, T.M., Kamagata, Y, Takami, H., and Saari, R.E. 1997. Biochemistry of 2,4-D degradation: evolutionary implications, In Microbial Diver-sity and Genetics of Biodegradation, pp. 35-51, K. Horikoshi, M. Fukuda, and T. Kudo, Eds., Japan Scientific Press, Tokyo.
   Google Scholar
• Hautala, T., Byers, M.G., Eddy, R.L., Shows, T.B., Kivirikko, K.I., and Myllyla, R. 1992. Cloning of human lysyl hydroxylase: com-plete cDNA-derived amino acid sequence and assignment of the gene (PLOD) to chromosome 1p36.1-p36.2. Genomics 13:62-69.
   Google Scholar
• Hazell, A., McKensie, C.J., Nielsen, L.P, Schindler, S., and Weitzer, M. 2002. Mononuclear non-heme iron(III) peroxide complexes: syntheses, characterization, mass spectrometric and kinetic studies. J Chem Soc Dalton Trans 310-317.
   Google Scholar
• Hedden, P. 1997. The oxidases of gibberellin biosynthesis: their func-tion and mechanism. Physiol Plant 101:709-719.
   Google Scholar
• Hedden, P. 1999. Recent advances in gibberellin biosynthesis. J Exper Bot 50:553-563.
   Google Scholar
• Hedden, P. and Kamiya, Y. 1997. Gibberellin biosynthesis: enzymes, genes and their regulation. Annu Rev Plant Physiol Plant Molec Biol 48:431-460.
   Google Scholar
• Hedden, P. and Phillips, A.L. 2000. Gibberellin metabolism: new in-sights revealed by the genes. Trend Plant Sci 5:523-528.
   Google Scholar
• Hegg, E.L., Ho, R.Y.N., and Que, L., Jr. 1999a. Oxygen activation and arene hydroxylation by functional mimics of a-keto acid-dependent iron(II) dioxygenases. JAm Chem Soc 121:1972-1973.
   Google Scholar
• Hegg, E.L., Whiting, A.K., Saari, R.E., McCracken, J., Hausinger, R.P, and Que, L., Jr. 1999b. Herbicide-degrading a-keto acid-dependent enzyme TfdA: metal coordination environment and mechanistic in-sights. Biochemistry 38:16714-16726.
   Google Scholar
• Helaakoski, T., Vuori, K., Myllyla, R., Kivirikko, K.I., andPihlajaniemi, T. 1989. Molecular cloning of the a-subunit of human prolyl 4-hydroxylase: the complete cDNA-derived amino acid sequence and evidence for alternative splicing of RNA transcripts. Proc Natl Acad Sci USA 86:4392-4396.
   Google Scholar
• Henshaw, T.F., Feig, M., and Hausinger, R.P. 2004. Aberrant activity of the DNA repair enzyme AlkB. J Inorg Biochem in press: Hewitson, K.S., McNeill, L.A., Elkins, J.M., and Schofield, C.J. 2003. The role of iron and 2-oxoglutarate oxygenases in signalling. Biochem Soc Trans 31:510-515.
   Google Scholar
• Hewitson, K.S., McNeill, L.A., Riordan, M.V., Tian, Y.-M., Bullock, A.N., Welford, R.W., Elkins, J.M., Oldham, N.J., Bhattacharya, S., Gleadle, J.M., Ratcliffe, P.J., Pugh, C.W., and Schofield, C.J. 2002. Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural familly. J Biol Chem 277:26351-26355.
   Google Scholar
• Hieta, R. and Myllyharju, J. 2002. Cloning and characterization of a low molecular weight prolyl 4-hydroxylase from Arabidopsis thaliana. Effective hydroxylation of proline-rich, collagen-like, and hypoxia-inducible transcription factor a-like peptides. J Biol Chem 277:23965-23971.
   Google Scholar
• Ho, R.Y.H., Roelfe, G., Hermant, R., Hage, R., Feringa, B.L., and Que, L., Jr. 1999a. Resonance Raman evidence for the interconversion be-tween an [FeIII-nI-O2]+ species and mechanistic implications thereof. Chem Commun 2161-2162.
   Google Scholar
• Ho, R.Y.N., Mehn, M.P, Hegg, E.L., Liu, A., Ryle, M.A., Hausinger, R.P, and Que, L., Jr. 2001. Resonance Raman studies of the iron(II)-a-keto acid chromophore in model and enzyme complexes. J Am Chem Soc 123:5022-5029.
   Google Scholar
• Ho, R.Y.N., Roelfes, G., Feringa, B.L., and Que, L., Jr. 1999b. Ra-man evidence for a weakened O-O bond in mononuclear low-spin iron(III)-hydroperoxides. J Am Chem Soc 121:264-265.
   Google Scholar
• Hogan, D.A., Auchtung, T.A., and Hausinger, R.P. 1999. Cloning and characterization of a sulfonate/a-ketoglutarate dioxygenase from Saccharomyces cerevisiae. J Bacteriol 181:5876-5879.
   Google Scholar
• Hogan, D.A., Smith, S.R., Saari, E.A., McCracken, J., and Hausinger, R.P. 2000. Site-directed mutagenesis of 2,4-dichlorophenoxyacetic acid/a-ketoglutarate dioxygenase. Identification of residues involved in metallocenter formation and substrate binding. J Biol Chem 275:12400-12409.
   Google Scholar
• Holme, E. 1975. A kinetic study of thymine 7-hydroxylase from Neu-rospora crassa. Biochemistry 14:4999-5003.
   Google Scholar
• Holme, E., Lindstedt, G., Lindstedt, S., and Tofft, M. 1971. 18O studies of the 2-ketoglutarate-dependent sequential oxygenation of thymine to 5-carboxyuracil. J Biol Chem 246:3314-3319.
   Google Scholar
• Holme, E., Lindstedt, S., and Nordin, I. 1984. Uncoupling and isotope effects in y-butyrobetaine hydroxylation. Biosci Rep 4:433-440.
   Google Scholar
• Holton, T.A., Brugliera, F., and Tanaka, Y. 1993. Cloning and expres-sion of flavonol synthase from Petunia hybrida. Plant J 4:1003-1010.
   Google Scholar
• Hon, W.-C, Wilson, M.I., Harlos, K., Claridge, T.D.W., Schofield, C.J., Pugh, C.W., Maxwell, P.H., Ratcliffe, P.J., Stuart, D.I., and Jones, E.Y 2002. Structural basis for the recognition of hydroxyproline in HIF-1a by pVHL. Nature 417:975-978.
   Google Scholar
• Hsu, C.-A., Saewert, M.D., Polsinelli, L.F., Jr., and Abbott, M.T. 1981. Uracil's uncoupling of the decarboxylation of a-ketoglutarate in the thymine 7-hydroxylase reaction of Neurospora crassa. J Biol Chem 256:6098-6101.
   Google Scholar
• Hubbard, B.K., Thomas, M.G., and Walsh, C.T. 2000. Biosynthesis of L-p-hydroxyphenylglycine, a non-proteinogenic amino acid constituent of peptide antibiotics. Chem Biol 7:931-942.
   Google Scholar
• Hulse, J.D., Ellis, S.R., and Henderson, L.M. 1978. Carnitine biosyn-thesis. -Hydroxylation of trimethyllysine by an -ketoglutarate-dependent mitochondrial dioxygenase. J Biol Chem 253:1654-1659.
   Google Scholar
• Hutton, J.J., Jr., Trappel, A.L., and Udenfriend, S. 1966. Requirement for -ketoglutarate, ferrous ion and ascorbate for collagen proline hydroxylase. Biochem Biophys Res Commun 24:179-184.
   Google Scholar
• Ince, N., de la Monte, S.M., and Wands, J.R. 2000. Overexpression of human aspartyl (asparaginyl) -hydroxylase is associated with malignant transformation. Cancer Res 60:1261-1266.
   Google Scholar
• Itoh, H., Ueguchi-Tanaka, M., Sentoku, N., Kitano, H., Matsuoka, M., and Kobayashi, M. 2001. Cloning and functional analysis of two gib-berellin 3-hydroxylase genes that are differently expressed during growth of rice. Proc Natl Acad Sci USA 98:8909-8914.
   Google Scholar
• Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J.M., Lane, W.S., and Kaelin, W.G., Jr. 2001. HIF targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 292:464-467.
   Google Scholar
• Jaakkola, P., Mole, D.R., Tian, Y.-M., Wilson, M.I., Gielbert, J., Gaskell, S.J., von Kriegsheim, A., Hebestreit, H.F., Mukherji, M., Schofield, C.J., Maxwell, P.H., Pugh, C.W., and Ratcliffe, P.J. 2001. Target-ing of HIF- to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292:468-472.
   Google Scholar
• Janc, J.W., Egan, L.A., and Townsend, C.A. 1995. Purification and char-acterization of clavaminate synthase from Streptomyces antibioti-cus. A multifunctional enzyme of clavam biosynthesis. J Biol Chem 270:5399-5404.
   Google Scholar
• Jansen, G.A., Mihalik, S.J., Watkins, P.A., Moser, H.W., Jakobs, C., Denis, S., and Wanders, R.J.A. 1996. Phytanoyl-CoA hydroxylase is present in human liver, located in peroxisomes, and deficient in Zell-weger syndrome: direct, unequivocal evidence for the new, revised pathway of phytanic acid -oxidation in humans. Biochem Biophys Res Commun 229:205-210.
   Google Scholar
• Jansen, G.A., Ofman, R., Denis, S., Ferdinandusse, S., Hogenhout, E.M., Jakobs, C., and Wanders, R.J.A. 1999. Phytanoyl-CoA hy-droxylase from rat liver: protein purification and cDNA cloning with implications for the subcellular localization of phytanic acid -oxidation. J Lipid Res 40:2244-2254.
   Google Scholar
• Jansen, G.A., Ofman, R., Ferdinandusse, S., Ijlst, L., Muijsers, A.O., Skjeldal, O.H., Stokke, O., Jakobs, C., Besley, G.T., Wraith, J.E., and Wanders, R.J.A. 1997. Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene. Nature Genet 17:190-193.
   Google Scholar
• Jensen, K.B., McKensie, C.J., Nielsen, L.P., Pedersen, J.Z., and Svendsen, H.M. 1999. Deprotonation of low-spin mononuclear iron(III)-hydroperoxide complexes give transient blue species as-signed to high-spin iron(III)-peroxide complexes. Chem Commun 1313-1314.
   Google Scholar
• Jensen, M.P., Lange, S.J., Mehn, M.P., Que, E.L., and Que, L., Jr. 2003. Biomimetic aryl hydroxylation derived from alkyl hydroperoxide at a nonheme iron center. Evidence for an FeIV = O oxidant. J Am Chem Soc 125:2113-2128.
   Google Scholar
• Jia, S., McGinnis, K., VanDusen, W.J., Burke, C.J., Kuo, A., Griffin, P.R., Sardana, M.K., Elliston, K.O., Stern, A.M., and Friedman, P.A. 1994. A fully active catalytic domain of bovine aspartyl (asparginyl) ß-hydroxylase expressed in Escherichia coli: characterization and evidence for the identification of an active-site region in vertebrate a-ketoglutarate-dependent dioxygenases. Proc Natl Acad Sci USA 91:7227-7231.
   Google Scholar
• Jia, S., VanDusen, W.J., Diehl, R.E., Kohl, N.E., Dixon, R.A.F., Elliston, K.O., Stern, A.M., and Friedman, P.A. 1992. cDNA cloning and expression of bovine aspartyl (asparginyl) /3-hydroxylase. J Biol Chem 267:14322-14327.
   Google Scholar
• Jiang, F., Peisach, J., Ming, L.-J., Que, L., Jr., and Chen, V.J. 1991. Electron spin echo envelope modulation studies of the Cu(I)-substituted derivative of isopenicillin N synthase: a structural and spectroscopic model. Biochemistry 30:11437-11445.
   Google Scholar
• Johnson-Winters, K., Purpero, V.M., Kavana, M., Nelson, T., and Moran, G.R. 2003. (4-Hydroxyphenyl)pyruvate dioxygenase from Streptomyces avermitilis: the basis for ordered substrate addition. Biochemistry 42:2072-2080.
   Google Scholar
• Jong, E. and Kemp, A. 1984. Stoichiometry and kinetics of the prolyl 4-hydroxylase partial reaction. Biochim Biophys Acta 787: 105-111.
   Google Scholar
• Kahnert, A. and Kertesz, M.A. 2000. Characterization of a sulfur-regulated oxygenative alkylsulfatase from Pseudomonas putida S-313. J Biol Chem 275:31661-31667.
   Google Scholar
• Kaska, D.D., Myllyla, R., Gunzler, V., Gibor, A., and Kivirikko, K.I. 1988. Prolyl 4-hydroxylase from Volvox carteri. A low-Mr enzyme antigenically related to the a subunit of the invertebrate enzyme. Biochem J 256:257-263.
   Google Scholar
• Kataoka, H. and Sekiguchi, M. 1985. Molecular cloning and charac-terization of the alkB gene of Escherichia coli. Molec Gen Genet 198:263-269.
   Google Scholar
• Kataoka, H., Yamamoto, Y., and Sekiguchi, M. 1983. A new gene (alkB) of Escherichia coli that controls sensitivity to methyl methane sul-fonate. J Bacteriol 153:1301-1307.
   Google Scholar
• Kawauchi, H., Tohno, M., Tsuchiya, Y, Hayashida, M., Adachi, Y, Mukai, T., Hayashi, I., Kimura, S., and Kondo, S. 1983. Studies on the structure of a novel peptide antibiotic, K-582. Int JPept Prot Res 21:546-554.
   Google Scholar
• Kertesz, M.A. 1999. Riding the sulfur cycle-metabolism of sulfonates and sulfate esters in Gram-negative bacteria. FEMS Microbiol Rev 24:135-175.
   Google Scholar
• Khaleeli, N., Busby, R.W., and Townsend, C.A. 2000. Site-directed mutagenesis and biochemical analysis of the endogenous ligands in the ferrous active site of clavaminate synthase. The His-3 variant of the 2-His-1-carboxylase model. Biochemistry 39:8666-8673.
   Google Scholar
• Kieliszewski, M.J. and Lamport, D.T. 1994. Extensin: repetitive mo-tifs, functional sites, post-translational codes, and phylogeny. Plant J 5:157-172.
   Google Scholar
• Kikuchi, Y, Suzuki, Y, and Tamiya, N. 1983. The source of oxygen in the reaction catalyzed by collagen lysyl hydroxylase. Biochem J 213:507-512.
   Google Scholar
• Kita, A., Kita, S.-I., Fujisawa, I., Inaka, K., Ishida, T., Horiike, K., Nozaki, M., and Miki, K. 1999. An archetypical extradiol-cleaving catecholic dioxygenase: the crystal structure of catechol 2,3-dioxygenase (metapyrocatechase) from Pseudomonas putida mt-2. Structure 7:25-34.
   Google Scholar
• Kivirikko, K.I. and Pihlajaniemi, T. 1998. Collagen hydroxylases and the protein disulfide isomerase subunit of prolyl 4-hydroxylase. Adv Enzymol Rel Areas Mol Biol 72:325-398.
   Google Scholar
• Koivisto, P., Duncan, T., Lindahl, T., and Sedgwick, B. 2003. Minimal methylated substrate and extended substrate range of Escherichia coli AlkB protein, a 1-methyladenine-DNA dioxygenase. J Biol Chem 278:44348-44354.
   Google Scholar
• Kondo, A., Blanchard, J.S., and Englard, S. 1981. Purification and properties of calf liver y-butyrobetaine hydroxylase. Arch Biochem Biophys 212:338-346.
   Google Scholar
• Kondo, H., Nakabeppu, Y., Kataoka, H., Kuhara, S., Kawabata, S., and Sekiguchi, M. 1986. Structure and expression of the alkB gene of Escherichia coli related to the repair of alkylated DNA. J Biol Chem 261:15772-15777.
   Google Scholar
• Korioth, F., Gieffers, C, and Frey, J. 1994. Cloning and characterization of the human gene encoding aspartyl /3-hydroxylase. Gene 150:395-399.
   Google Scholar
• Kovacevic, S., Weigel, B.J., Tobin, M.B., Ingolia, T.D., and Miller, J.R. 1989. Cloning, characterization, and expression in Escherichia coli of the Streptomyces clavuligerus gene encoding deacetoxy-cephalosporin C synthetase. J Bacteriol 171:754-760.
   Google Scholar
• Kreisberg-Zakarin, R., Borovok, I., Yanko, M., Aharonowitz, Y., and Cohen, G. 1999. Recent advances in the structure and function of isopenicillin N synthase. Antonie van Leeuwenhoek 75: 33-39.
   Google Scholar
• Kreisberg-Zakarin, R., Borovok, I., Yanko, M., Frolow, F., Aharonowitz, Y, and Cohen, G. 2000. Structure-function studies of non-heme iron active site of isopenicillin N synthase: some im-plications for catalysis. Biophys Chem 86:109-118.
   Google Scholar
• Kurowski, M.A., Bhagwat, A.S., Papaj, G., and Bujnicki, J.M. 2003. Phylogenomic identification of five new human homologues of the DNA repair enzyme AlkB. BMC Genomics 4:48.
   Google Scholar
• Lamberg, A., Pihlajaniemi, T., and Kivirikko, K.I. 1995. Site-directed mutagenesis of the a subunit of human prolyl 4-hydroxylase. Identification of three histidine residues critical for catalytic activity. J Biol Chem 270:9926-9931.
   Google Scholar
• Landman, O., Borovok, I., Aharonowitz, Y, and Cohen, G. 1997. The glutamine ligand in the ferrous iron active site of isopenicillin N synthase of Streptomyces jumonjinensis is not essential for catalysis. FEBS Lett 405:172-174.
   Google Scholar
• Lando, D., Peet, D.J., Whelan, D.A., Gorman, J.J., and Whitelaw, M.L. 2002. Asparagine hydroxylation of the HIF transactivation domain: a hypoxic switch. Science 295:858-861.
   Google Scholar
• Lange, T. 1994. Purification and partial amino-acid sequence of gib-berellin 20-oxidase from Cucurbita maxima L. endosperm. Planta 195:108-115.
   Google Scholar
• Lange, T. 1997. Cloning gibberellin dioxygenase genes from pump-kin endosperm by heterologous expression of enzyme activities in Escherichia coli. Proc Natl Acad Sci USA 94:6553-6558.
   Google Scholar
• Lange, T. and Graebe, J. E. 1989. The partial purification and charac-terization of a gibberellin C-20 hydroxylase from immature Pisum sativum L. seeds. Planta 179:211-221.
   Google Scholar
• Lange, T., Hedden, P., and Graebe, J.E. 1994a. Expression cloning of a gibberellin 20-oxidase, a multifunctional enzyme involved in gibberellin synthesis. Proc Natl Acad Sci USA 91:8552-8556.
   Google Scholar
• Lange, T., Kegler, C, Hedden, P., Phillips, A.L., and Graebe, J.E. 1997a. Molecular characterization of gibberellin 20-oxidases. Structure-function studies on recombinant enzymes and chimaeric proteins. Physiol Plant 100:543-549.
   Google Scholar
• Lange, T., Robatzek, S., andFrisse, A. 1997b. Cloning and expression of a gibberellin 2/3,3/3-hydroxylase cDNA from pumpkin endosperm. The Plant Cell 9:1459-1467.
   Google Scholar
• Lange, T., Schweimer, A., Ward, D.A., Hedden, P., and Graebe, J.E. 1994b. Separation and characterization of three 2-oxoglutarate-dependent dioxygenases from Cucurbita maxima L. endosperm involved in gibberellin biosynthesis. Planta 195:98-107.
   Google Scholar
• Lawrence, C.C., Sobey, W.J., Field, R.A., Baldwin, J.E., and Schofield, C.J. 1996. Purification and initial characterization of proline 4-hydroxylase from Streptomyces griseoviridus P8648: a 2-oxoacid, ferrous-dependent dioxygenase involved in etamycin biosynthesis. Biochem J313:185-191.
   Google Scholar
• Lay, V.J., Prescott, A.G., Thomas, P.G., and John, P. 1996. Het-erologous expression and site-directed mutagenesis of the 1-aminocyclopropane-1-carboxylate oxidase from kiwi fruit. Eur J Biochem 242:228-234.
   Google Scholar
• Le Marchand, L. 2002. Cancer prevention effects of flavonoids-a re-view. Biomed Pharmacother 56:296-301.
   Google Scholar
• Lee, C, Kim, S.J., Jeong, D.G., Lee, S.M., andRyu, S.E. 2003. Structure of human FIH-1 reveals a unique active site pocket and interaction sites for HIF-1 and von Hipple-Lindau. JBiol Chem 278:7558-7563.
   Google Scholar
• Lee, H.J., Lloyde, M.D., Clifton, I.J., Baldwin, J.E., and Schofield, C.J. 2001a. Kinetic and crystallographic studies on deacetoxy-cephalosporin C synthase (DAOCS). J Mol Biol 308:937-948.
   Google Scholar
• Lee, H.-J., Lloyd, M.D., Clifton, I.J., Harlos, K., Dubus, A., Baldwin, J.E., Frere, J.-M., and Schofield, C.J. 2001b. Alteration of the co-substrate selectivity of deacetoxycephalosporin C synthase. The role of arginine 258. J Biol Chem 276:18290-18295.
   Google Scholar
• Lee, H.J., Schofield, C.J., and Lloyde, M.D. 2002. Active site muta-tions of recombinant deacetoxycephalosporin C synthase. Biochem Biophys Res Commun 292:66-70.
   Google Scholar
• Lester, D.R., Ross, J.J., Davies, P.J., and Reid, J.B. 1997. Mendel's stem length gene (Le) encodes a gibberellin 3/3-hydroxylase. The Plant Cell 9:1435-1443.
   Google Scholar
• Lester, D.R., Ross, J.J., Smith, J.J., Elliott, R.C., and Reid, J.B. 1999. Gibberellin 2-oxidation and the SLN gene of Pisum sativum. Plant J 19:65-73.
   Google Scholar
• Lim, M.H., Rohde, J.-U., Stubna, A., Bukowski, M.R., Costas, M., Ho, R.Y.N., Munck, E., Nam, W., and Que, L., Jr. 2003. An FeIV = O complex of a tetradentate tripodal nonheme ligand. Proc Natl Acad Sci USA 100:3665-3670.
   Google Scholar
• Lindblad, B., Lindstedt, G., and Lindstedt, S. 1970. The mechanism of enzymic formation of homogentisate from p-hydroxyphenyl-pyruvate. J Am Chem Soc 92:7446-7449.
   Google Scholar
• Lindblad, B., Lindstedt, G., Lindstedt, S., and Rundgren, M. 1977. Purification and some properties of human 4-hydroxyphenylpyruvate dioxygenase. J Biol Chem 252:5073-5084.
   Google Scholar
• Lindblad, B.G.L., Tofft, M., and Lindstedt, S. 1969. The mechanism of a-ketoglutarate oxidation in coupled enzymatic oxygenations. J Am Chem Soc 91:4604-4606.
   Google Scholar
• Lindstedt, G., Lindstedt, S., and Nordin, I. 1977. Purification and properties of y-butyrobetaine hydroxylase from Pseudomonas sp. AK1. Biochemistry 16:2181-2188.
   Google Scholar
• Lindstedt, S. and Rundgren, M. 1982. Blue color, metal content, and substrate binding in 4-hydroxyphenylpyruvate dioxygenase from Pseudomonas sp. strain P. J. 874. J Biol Chem 257:11922-11931.
   Google Scholar
• Lipscomb, S.J., Lee, H.-J., Mukherji, M., Baldwin, J.E., Schofield, C.J., and Lloyd, M.D. 2002. The role of arginine residues in substrate binding and catalysis by deacetoxycephalosporin C synthase. Eur J Biochem 269:2735-2739.
   Google Scholar
• Liu, A., Ho, R.Y.N., Que, L., Jr., Ryle, M.J., Phinney, B.S., and Hausinger, R.P 2001. Alternative reactivity of an a-ketoglutarate-dependent iron(II) oxygenase: enzyme self-hydroxylation. J Am Chem Soc 123:5126-5127.
   Google Scholar
• Lloyd, M.D., Lee, H.-J., Harlos, K., Zhang, Z.-H., Baldwin, J.E., Schofield, C.J., Charnock, J.M., Garner, CD., Hara, T., Terwisscha Van Scheltinga, A.C., Valegard, K., Viklund, J.A.C., Hajdu, J., Andersson, I., Danielsson, A., and Bhikhabhai, R. 1999a. Studies on the active site of deacetoxycephalosporin C synthase. J MolBiol 287:943-960.
   Google Scholar
• Lloyd, M.D., Merrit, K.D., Lee, V., Sewell, T.J., Wha-Son, B., Baldwin, J.E., Schofield, C.J., Elson, S.W., Baggaley, K.H., and Nicholson, N.H. 1999b. Product-substrate engineering by bacteria: studies on clavaminate synthase, a trifunctional dioxygenase. Tetra-hedron 55:10201-10220.
   Google Scholar
• Lloyd, M.D., Lipscomb, S.J., Hewitson, K.S., Hensgenes, CM., Baldwin, J.E., and Schofield, C.J. 2004. Controlling the substrate selectivity of deacetoxy/deacetylcephalosporin C synthase. J Biol Chem, In press.
   Google Scholar
• Long, A.J., Clifton, I.J., Roach, P.L., Baldwin, J.E., Schofield, C.J., and Rutledge, P.J. 2003. Structural studies on the reaction of isopeni-cillin N synthase with the substrate analogue (L-a-aminoadipoyl)-L-cysteinyl-D-a-aminobutyrate. Biochem J372:687-693.
   Google Scholar
• Lukacin, R. and Britsch, L. 1997. Identification of strictly conserved histidine and arginine residues as part of the active site in Petu-nia hybrida flavanone 3ß-hydroxylase. Eur J Biochem 249:748-757.
   Google Scholar
• Lukacin, R., Groning, I., Pieper, U., and Matern, U. 2000a. Site-directed mutagenesis of the active site serine290 in flavanone 3/3-hydroxylase from Petunia hybrida. Eur J Biochem 267:853-860.
   Google Scholar
• Lukacin, R., Groning, I., Schiltz, E., Britsch, L., and Matern, U. 2000b. Purification of recombinant flavanone 3/3-hydroxylase from Petunia hybrida and assignment of the primary site of proteolytic degradation. Arch Biochem Biophys 375:364-370.
   Google Scholar
• Lukacin, R., Wellman, F., Britsch, L., Martens, S., and Matern, U. 2003. Flavonol synthase from Citrus unshiu is a bifunctional dioxygenase. Phytochem 62:287-292.
   Google Scholar
• MacBeth, CE., Golombek, A.P, Young, V.G., Jr., Yang, C, Kuczera, K., Hendrich, M.P, and Borovik, A.S. 2000. O2 activation by non-heme iron complexes: a monomeric Fe(III)-oxo complex derived from O2. Science 289:938-941.
   Google Scholar
• Mahon, P.C., Hirota, K., and Semenza, G.L. 2001. FIH-1: anovelpro-tein that interacts with HIF-1a and VHL to mediate repression of HIF-1 transcriptional activity. Genes Dev 15:2675-2686.
   Google Scholar
• Mao, Y, Varoglu, M., and Sherman, D.H. 1999. Molecular characteri-zation and analysis of the biosynthetic gene cluster for the antitumor antibiotic mitomycin C from Streptomyces lavendulae 2564. Chem Biol 6:251-263.
   Google Scholar
• Marsh, E.N., Chang, M.D.-T., andTownsend, C.A. 1992. Two isozymes of clavaminate synthase central to clavulanic acid formation: cloning and sequencing of both genes from Streptomyces clavuligerus. Biochemistry 31:12648-12657.
   Google Scholar
• Martens, S., Forkmann, G., Britsch, L., Wellmann, F, Matern, U., and Lukacin, R. 2003. Divergent evolution of flavonoid 2-oxoglutarate-dependent dioxygenases in parsley. FEBS Lett 544:93-98.
   Google Scholar
• Martens, S., Forkmann, G., Matern, U., and Lukacin, R. 2001. Cloning of parsley flavone synthase I. Phytochem 58:43-46.
   Google Scholar
• Martin, D.N., Proebsting, W.M., and Hedden, P. 1997. Mendel's dwarf-ing gene: cDNAs from the Le alleles and function of the expressed proteins. Proc Natl AcadSci USA 94:8907-8911.
   Google Scholar
• Martinkus, K.J., Tann, C.-H., and Gould, S.J. 1983. The biosynthesis of the streptolidine moiety in streptothricin F. Tetrahedron 39:3493- 3505.
   Google Scholar
• Masson, N., William, C., Maxwell, P.H., Pugh, C.W., and Ratcliffe, P.J. 2001. Independent function of two destructive domains in hypoxia-inducible factor- chains activated by prolyl hydroxylation. EMBO J 20:5197-5206.
   Google Scholar
• Matsuda, J., Okabe, S., Hashimoto, T., and Yamada, Y. 1991. Molec-ular cloning of hyoscyamine 6-hydroxylase, a 2-oxoglutarate-dependent dioxygenase, from cultured roots of Hyoscyamus niger. J Biol Chem 266:9460-9464.
   Google Scholar
• McGinnis, K., Ku, G.M., VanDusen, W.J., Fu, J., Garsky, V., Stern, A.M., and Friedman, P.A. 1996. Site-directed mutagenesis of residues in a conserved region of bovine aspartyl (asparaginyl) ß-hydroxylase: evidence that histidine 675 has a role in binding Fe2+. Biochemistry 35:3957-3962.
   Google Scholar
• McGowan, S.J., Sebaihia, M., Porter, L.E., Stewart, G.S., Williams, P., Bycroft, B.W., and Salmond, G.P. 1996. Analysis of bacterial carbapenam antibiotic production genes reveals a novel -lactam biosynthesis pathway. Molec Microbiol 22:415-426.
   Google Scholar
• McNeill, L.A., Hewitson, K.S., Claridge, T.D., Seibel, J.F., Horsfall, L.E., and Schofield, C.J. 2002a. Hypoxia-inducible factor asparginyl hydroxylase (FIH-1) catalyses hydroxylation at the -carbon of asparagine-803. Biochem J 367:571-575.
   Google Scholar
• McNeill, L.A., Hewitson, K.S., Gleadle, J.M., Horsfall, L.E., Oldham, N.J., Maxwell, P.H., Pugh, C.W., Ratcliffe, P.J., and Schofield, C.J. 2002b. The use of dioxygen by HIF prolyl hydroxylase (PHD1). Bioorg Med Chem Lett 12:1547-1550.
   Google Scholar
• Mehn, M.P., Fujisawa, K., Hegg, E.L., and Que, L., Jr. 2003. Oxygen activation by nonheme iron(II) complexes: -keto carboxylate versus carboxylate. J Am Chem Soc 124:7828-7842.
   Google Scholar
• Metcalf, W.W. and Wolfe, R.S. 1998. Molecular genetic analysis of phosphite and hypophosphite oxidation by Pseudomonas stutzeri WM88. J Bacteriol 180:5547-5558.
   Google Scholar
• Mihalik, S.J., Morrell, J.C., Kim, D., Sacksteder, K.A., Watkins, P.A., and Gould, S.J. 1997. Identification ofPAHX,aRefsum disease gene. Nature Genet 17:185-189.
   Google Scholar
• Mihalik, S.J., Rainville, A.M., and Watkins, P.A. 1995. Phytanic acid -oxidation in rat liver peroxisomes. Production of -hydroxyphytanoyl-CoA and formate is enhanced by dioxygenase cofactors. Eur J Biochem 232:545-551.
   Google Scholar
• Min, J.-H., Yang, H., Ivan, M., Gertler, F., Kaelin, W.G., Jr., and Pavletich, N.P. 2002. Structure of an HIF-1-pVHL complex: hy-droxyproline recognition in signaling. Science 296:1886-1889.
   Google Scholar
• Min, W.-C., Begley, T.J., Myllyharju, J., and Kivirikko, K.I. 2000. Mechanistic studies on prolyl-4-hydroxylase: demonstration that the ferryl intermediate does not exchange with water. Bioorgan Chem 28:261-265.
   Google Scholar
• Minchenko, A., Leshchinsky, I., Opentanova, I., Sang, N., Srinivas, V., Armstead, V., and Caro, J. 2002. Hypoxia-inducible factor-1-mediated expression of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphate (PFKFB3) gene. Its possible role in the Warburg effect. J Biol Chem 277:6183-6187.
   Google Scholar
• Ming, L.-J., Que, L., Jr., Kriauciunas, A., Frolik, C.A., and Chen, V.J. 1990. Coordination chemistry of the metal binding site of isopeni-cillin N synthase. Inorg Chem 29:1111-1112.
   Google Scholar
• Ming, L.-J., Que, L., Jr., Kriauciunas, A., Frolik, C.A., and Chen, V.J. 1991. NMR studies of the active site of isopenicillin N synthase, a non-heme iron(II) enzyme. Biochemistry 30:11653-11659.
   Google Scholar
• Mishina, Y. and He, C. 2003. Probing the structure and function of the Escherichia coli DNA alkylation repair AlkB protein through chemical cross-linking. J Am Chem Soc 125:8730-8731.
   Google Scholar
• Mishina, Y., Lee, C.-H.J., and He, C. 2004. Interaction of human and bacterial AlkB proteins with DNA as probed through chemical cross-linking studies. Nucleic Acids Res 32:1548-1554.
   Google Scholar
• Mori, H., Shibasaki, T., Uozaki, Y, Ochiai, K., and Ozaki, A. 1996. Detection of novel proline 3-hydroxylase activities in Streptomyces and Bacillus spp. by regio- and stereospecific hydroxylation of L-proline. Appl Environ Microbiol 62:1903-1907.
   Google Scholar
• Mori, H., Shibasaki, T., Yano, K., and Ozaki, A. 1997. Purification and cloning of a proline 3-hydroxylase, a novel enzyme which hy-droxylates free L-proline to cis-3-hydroxy-L-proline. J Bacteriol 179:5677-5683.
   Google Scholar
• Mukherji, M., Kershaw, N.J., Schofield, C.J., Wierzbicki, A.S., and Lloyd, M.D. 2002. Utilization of sterol carrier protein-2 by phytanoyl-CoA 2-hydroxylase in the peroxisomal oxidation of phytanic acid. Chem Biol 9:597-605.
   Google Scholar
• Mukherji, M., Schofield, C.J., Wierzbicki, A.S., Jansen, G.A., Wanders, R.J.A., and Lloyd, M.D. 2003. The chemical biology of branched-chain lipid metabolism. Prog Lipid Res 42:359-376.
   Google Scholar
• Mukherji, M., Chien, W., Kershaw, N.J., Clifton, I.J., Schofield, C.J., Wierzbicki, A.S., and Lloyd, M.D. 2001a. Structure-function anal-ysis of phytanoyl-CoA 2-hydroxylase mutations causing Refsum's disease. Human Molec Genet 10:1971-1982.
   Google Scholar
• Mukherji, M., Kershaw, N.J., MacKinnon, C.H., Clifton, I.J., Wierzbicki, A.S., Schofield, C.J., andLloyd, M.D. 2001b. "Chemical co-substrate rescue" of phytanoyl-CoA hydroxylase mutants causing Refsum's disease. Chem Commun 972-973.
   Google Scholar
• Muller, I., Kahnert, A., Pape, T., Sheldrick, G.M., Meyer-Klaucke, W., Dierks, T., Kertesz, M., and Uson, I. 2004. Crystal structure of the alkylsulfatase AtsK: insights into the catalytic mechanism of the Fe(II), -ketoglutarate dependent dioxygenase superfamily. Biochemistry 43:3075-3088.
   Google Scholar
• Myllyharju, J. and Kivirikko, K.I. 1997. Characterization of the iron-and 2-oxoglutarate-binding sites of human prolyl 4-hydroxylase. EMBO J 16:1173-1180.
   Google Scholar
• Myllyla, R., Kuutti-Saolainen, E.-R., and Kivirikko, K.I. 1978. The role of ascorbate in the prolyl hydroxylase reaction. Biochem Biophys Res Commun 83:441-448.
   Google Scholar
• Myllyla, R., Majamaa, K., Gunzler, V., Hanauske-Abel, H.N., and Kivirikko, K.I. 1984. Ascorbate is consumed stoichiometrically in the uncoupled reactions catalyzed by prolyl 4-hydroxylase and lysyl hydroxylase. J Biol Chem 259:5403-5405.
   Google Scholar
• Nagahama, K., Ogawa, T., Fujii, T., Tazaki, M., Goto, M., and Fukuda, H. 1991a. L-Arginine is essential for the formation in vitro of ethylene by an extract of Pseudomonas syringae. J Gen Microbiol 137:1641-1646.
   Google Scholar
• Nagahama, K., Ogawa, T., Fujii, T., Tazaki, M., Tanase, S., Morino, Y, and Fukuda, H. 1991b. Purification and properties of an ethylene-forming enzyme from Pseudomonas syringae pv. phaseolica PK2. J Gen Microbiol 137:2281-2286.
   Google Scholar
• Nagahama, K., Yoshini, K., Matsuoka, M., Tanase, S., Ogawa, T., and Fukuda, H. 1998. Site-directed mutagenesis of histidine residues in the ethylene-forming enzyme from Pseudomonas syringae. J Ferm Bioeng 85:255-258.
   Google Scholar
• Nakajima, J.-I., Yoshikaru, Y, Yamazaki, M., and Saito, K. 2001. Reaction mechanism from leucoanthocyanidin to anthocyanidin 3-glucoside, a key reaction for coloring in anthocyanin biosynthesis. J Biol Chem 276:25797-25803.
   Google Scholar
• Nickel, K., Suter, M.J.-F., and Kohler, H.-P.E. 1997. Involvement of two -ketoglutarate-dependent dioxygenases in enantioselective degradation of (R)- and (S)-mecoprop by Sphingomonas herbicidovorans MH. J Bacteriol 179:6674-6679.
   Google Scholar
• Brien, J.R., Schuller, D.J., Yang, V.S., Dillard, B.D., and Lanzilotta, W.N. 2003. Substrate-induced conformational changes in Escherichia coli taurine/-ketoglutarate dioxygenase and insight into the oligomeric structure. Biochemistry 42:5547-5554.
   Google Scholar
• Oehme, F., Ellinghaus, P., Kolkhof, P., Smith, T.J., Ramakrishnan, S., Hutter, J., Schramm, M., and Flamme, I. 2002. Overexpression of PH-4, a novel putative proline 4-hydroxylase, modulates activity of hypoxia-inducible transcription factors. Biochem Biophys Res Commun 296:343-349.
   Google Scholar
• Ogle, J.M., Clifton, I.J., Rutledge, P.J., Elkins, J.M., Burzlaff, N.I., Adlington, R.M., Roach, PL., and Baldwin, J.E. 2001. Alternative oxidation by isopenicillin N synthase observed by X-ray diffraction. Chem Biol 8:1231-1237.
   Google Scholar
• Omura, S., Tomoda, H., Yamamoto, S., Tsukui, M., and Tanaka, H. 1984. Studies on two dioxygenases involved in the synthesis of tylosin in Streptomyces fradiae. Biochim Biophys Acta 802:141-147.
   Google Scholar
• Park, M.H., Wolff, E.C., and Folk, J.E. 1993. Hypusine: its post-translational formation in eukaryotic initiation factor 5A and its po-tential role in cellular regulation. Biofactors 4:95-104.
   Google Scholar
• Park, J.H., Wolff, E.C., Folk, J.E., and Park, M.H. 2003. Reversal of the deoxyhypusine synthesis reaction. Generation of spermidine or homospermidine from deoxyhypusine by deoxyhypusine synthase. J Biol Chem 278:32683-32691.
   Google Scholar
• Passoja, K., Myllyharju, J., Pirskanen, A., and Kivirikko, K.I. 1998a. Identification of arginine-700 as the residue that binds the C-5 car-boxyl group of 2-oxoglutarate in human lysyl hydroxylase 1. FEBS Lett 434:145-148.
   Google Scholar
• Passoja, K., Rautavuoma, K., Ala-Kokko, L., Kosonen, T., and Kivirikko, K.I. 1998b. Cloning and characterization of a third human lysyl hydroxylase isoform. Proc Natl Acad Sci USA 95:10482-10486.
   Google Scholar
• Pavel, E.G., Zhou, J., Busby, R.W., Gunsior, M., Townsend, C.A., and Solomon, E.I. 1998. Circular dichroism and magnetic circu-lar dichroism spectroscopic studies of the non-heme ferrous active site in clavaminate synthase and its interaction with -ketoglutarate cosubstrate. J Am Chem Soc 120:743-753.
   Google Scholar
• Pekkala, M., Hieta, R., Kursula, P., Kivirikko, K.I. Wierenga, R.K., and Myllyharju, J. 2003. Crystallization of the proline-rich-peptide binding domain of human type I collagen prolyl 4-hydroxylase. Acta Cryst D59:940-942.
   Google Scholar
• Pelletier, M.K. and Shirley, B.W. 1996. Analysis of flavanone 3-hydroxylase in Arabidopsis seedlings. Plant Physiol 111:339-345.
   Google Scholar
• Petersen, L., Olewinski, R., Salmon, P., and Conners, N. 2003. Novel proline hydroxylase activities in the pneumocandin-producing fun-gus Glarea lozoyensis responsible for the formation of trans 3- and trans 4-hydroxyproline. Appl Microbiol Biotechnol 62:263-267.
   Google Scholar
• Pirrung, M.C., Cao, J., and Chen, J.1998. Ethylene biosynthesis: pro-cessing of a substrate analog supports a radical mechanism for the ethylene-forming enzyme. Chem Biol 5:49-57.
   Google Scholar
• Pirrung, M.C., Kaiser, L.M., and Chen, J. 1993. Purification and prop-erties of the apple fruit ethylene-forming enzyme. Biochemistry 32:7445-7450.
   Google Scholar
• Pirskanen, A., Kaimio, A.-M., Myllyla, R., and Kivirikko, K.I. 1996. Site-directed mutagenesis of human lysyl hydroxylase expressed in insect cells. Identification of histidine residues and an aspartic acid residue critical for catalytic activity. J Biol Chem 271:9398-9402.
   Google Scholar
• Poneleit, L.S. and Dilley, D.R. 1993. Carbon dioxide activation of 1-aminocyclopropane-1-carboxylate (ACC) oxidase in ethylene biosynthesis. Postharvest Biol Technol 3:191-199.
   Google Scholar
• Prescott, A.G. 1993. A dilemma of dioxygenases (or where biochem-istry andmolecular biology fail to meet). J Exper Bot 44:849-861.
   Google Scholar
• Prescott, A.G. and Lloyd, M.D. 2000. The iron(II) and 2-oxoacid-dependent dioxygenases and their role in metabolism. Nat Prod Rep 17:367-383.
   Google Scholar
• Prescott, A.G., Stamford, N.P.J., Wheeler, G., and Firmin, J.L. 2002. In vitro properties of a recombinant flavonol synthase from Ara-bidopsis thaliana. Phytochem 60:589-593.
   Google Scholar
• Price, J.C., Barr, E.W., Glass, T.E., Krebs, C, and Bollinger, J.M., Jr. 2003a. Evidence for hydrogen abstraction from C1 of taurine by the high-spin Fe(IV) intermediate detected during oxygen activation by taurine:a-ketoglutarate dioxygenase (TauD). J Am Chem Soc 125:13008-13009.
   Google Scholar
• Price, J.C., Barr, E.W., Tirupati, B., Bollinger, J.M., Jr., and Krebs, C. 2003b. The first direct characterization of a high-valent iron interme-diate in the reaction of an a-ketoglutarate-dependent dioxygenase: a high-spin Fe(IV) complex in taurine/a-ketoglutarate dioxygenase (TauD) from Escherichia coli. Biochemistry 42:7497-7508.
   Google Scholar
• Proshlyakov, D.A., Henshaw, T.F., Monterosso, G.R., Ryle, M.J., and Hausinger, R.P 2004. Direct detection of oxygen intermediates in the non-heme Fe enzyme taurine/a-ketoglutarate dioxygenase. J Am Chem Soc 126:1022-1023.
   Google Scholar
• Puistola, U., Turpeenniemi-Hujanen, T.M., Myllyla, R., and Kivirikko, K. 1980. Studies on the lysyl hydroxylase reaction. 1. Initial velocity kinetics and related aspects. Biochim Biophys Acta 611:40-50.
   Google Scholar
• Randall, C.R., Zang, Y., True, A.E., Que, L., Jr., Charnock, J.M., Garner, CD., Fujishima, Y., Schofield, C.J., and Baldwin, J.E. 1993. X-ray absorption studies of the ferrous active site of isopenicillin N synthase and related model complexes. Biochemistry 32:6664-6673.
   Google Scholar
• Rao, N.V. and Adams, E. 1978. Partial reaction of prolyl hydroxylase. (Gly-Gly-Pro)n stimulates a-ketoglutarate decarboxylation without prolyl hydroxylase. J Biol Chem 253:6327-6330.
   Google Scholar
• Risteli, J., Tryggvason, K., and Kivirikko, K.I. 1977. Prolyl 3-hydroxylase: partial purification of the enzyme from rat kidney cortex. Eur J Biochem 73:485-492.
   Google Scholar
• Roach, PL., Clifton, I.J., Fulop, V., Harlos, K., Barton, G.J., Hajdu, J., Andersson, K., Schofield, C.J., and Baldwin, J.E. 1995. Crystal structure of isopenicillin N synthase is the first from a new structural family of enzymes. Nature (London) 375:700-704.
   Google Scholar
• Roach, PL., Clifton, I.J., Hensgens, C.M.H., Shibata, N., Schofield, C.J., Hajdu, J., and Baldwin, J.E. 1997. Structure of isopenicillin N synthase complexed with substrate and the mechanism of penicillin formation. Nature (London) 387:827-830.
   Google Scholar
• Rocklin, A.M., Tierney, D.L., Kofman, V., Brunhuber, N.M.W., Hoffman, B.M., Christoffersen, R.E., Reich, N.O., Lipscomb, J.D., and Que, L., Jr. 1999. Role of the nonheme Fe(II) center in the biosynthesis of the plant hormone ethylene. Proc Natl Acad Sci USA 96:7905-7090.
   Google Scholar
• Roelfes, G., Lubben, M., Chen, K., Ho, R.Y.N., Meetsma, A., Genseberger, S., Hermant, R.M., Hage, R., Mandal, S.K., Young, V.G., Jr., Zang, Y, Kooijman, H., Spek, A.L., Que, L., Jr., and Feringa, B.L. 1999. Iron chemistry of a pentadentate ligand that gen-erates a metastable FeIII-OOH intermediate. Inorg Chem 38:1929-1936.
   Google Scholar
• Roelfes, G., Lubben, M., Hage, R., Que, L., Jr., and Feringa, B.L. 2000. Catalytic oxidation with a non-heme iron complex that generates a low-spin FeIIIOOH intermediate. Chem Eur J 6:2152-2159.
   Google Scholar
• Rohde, J.-U., In, J.-H., Lim, M.H., Brennessel, W.W., Bukowski, M.R., Stubna, A., Munck, E., and Que, L., Jr. 2003. Crystallographic and spectroscopic characterization of a nonheme Fe(IV)=O complex. Science 299:1037-1039.
   Google Scholar
• Ruetschi, U., Nordin, I., Odelhog, B., Jornvall, H., and Lindstedt, S. 1993. y-Butyrobetaine hydroxylase. Structural characterization of the Pseudomonas enzyme. Eur J Biochem 213:1075-1080.
   Google Scholar
• Ryle, M.J. and Hausinger, R.P. 2002. Non-heme iron oxygenases. Curr Opinion Chem Biol 6:193-201.
   Google Scholar
• Ryle, M.J., Koehntop, K.D., Liu, A., Que, L., Jr., and Hausinger, R.P. 2003a. Interconversion of two oxidized forms of TauD, a non-heme iron hydroxylase: evidence for bicarbonate binding. Proc Natl Acad Sci USA 100:3790-3795.
   Google Scholar
• Ryle, M.J., Liu, A., Muthukumaran, R.B., Ho, R.Y.N., Koehntop, K.D., McCracken, J., Que, L., Jr., and Hausinger, R.P. 2003b. O2- and a-ketoglutarate-dependent tyrosyl radical formation in TauD, an a-keto acid-dependent non-heme iron dioxygenase. Biochemistry 42:1854-1862.
   Google Scholar
• Ryle, M.J., Padmakumar, R., and Hausinger, R.P. 1999. Stopped-flow kinetic analysis of Escherichia coli taurine/a-ketoglutarate dioxygenase: interactions with a-ketoglutarate, taurine, and oxygen. Biochemistry 38:15278-15286.
   Google Scholar
• Saari, R.E. and Hausinger, R.P. 1998. Ascorbic acid-dependent turnover and reactivation of 2,4-dichlorophenoxyacetic acid/a-ketoglutarate dioxygenase using thiophenoxyacetic acid. Biochemistry 37:3035-3042.
   Google Scholar
• Saari, R.E., Hogan, D.A., and Hausinger, R.P. 1999. Stereospe-cific degradation of the phenoxypropionate herbicide dichlorprop. JMolec Catalysis B 6:421-428.
   Google Scholar
• Sabourin, PJ. and Bieber, L.L. 1982. The mechanism of a-ketoisocaproate oxygenase. Formation of/3-hydroxyisovalerate from a-ketoisocaproate. J Biol Chem 257:7468-7471.
   Google Scholar
• Saito, K., Kobayashi, M., Gong, Z., Tanaka, Y, and Yamazaki, M. 1999. Direct evidence for anthocyanidin synthase as a 2-oxoglutarate-dependent oxygenase: molecular cloning and functional expression of cDNA from a red forma of Perilla fructescens. Plant J 17:181- 189.
   Google Scholar
• Sami, M., Brown, T.J.N., Roach, PL., Schofield, C.J., and Baldwin, J.E. 1997. Glutamine-330 is not essential for activity in isopenicillin N synthase from Aspergillus nidulans. FEBS Lett 405:191-194.
   Google Scholar
• Samson, S.M., Belagaje, R., Blankenship, D.T., Chapman, J.L., Perry, D., Skatrud, PL., VanFrank, R., Abraham, E.P, Baldwin, J.E., Queener, S.W., and Ingolia, T.D. 1985. Isolation, sequence determi-nation and expression in Escherichia coli of the isopenicillin N syn-thetase gene from Cephalosporium acremonium. Nature (London) 318:191-194.
   Google Scholar
• Petit, P., Broca, C, Manteghetti, M., Baissac, Y, Fernandez-Alverez, J., Gross, R., Roye, M., Leconte, A., Gomis, R., and Ribes, G. 1998. 4-Hydroxyisoleucine: a novel amino acid potentiator of insulin secretion. Diabetes 47:206-210.
   Google Scholar
• Schofield, C.J., Baldwin, J.E., Byford, M.F., Clifton, I.J., Hensgens, C, and Roach, P.L. 1997. Proteins of thepenicillin biosynthesis pathway. Curr Opinion Struct Biol 7:857-864.
   Google Scholar
• Zhang, Z. 1999. Structural and mechanistic studies on 2-oxoglutarate-dependent oxygenases and related enzymes. Curr Opinion Struct Biol 9:722-731.
   Google Scholar
• Schomburg, F.M., Bizzell, CM., Lee, D.J., Zeevaart, J.A.D., and Amasino, R.M. 2003. Overexpression of a novel class of gibberellin 2-oxidases decreases gibberellin levels and creates dwarf plants. The Plant Cell 15:151-163.
   Google Scholar
• Scott, R.A., Wang, S., Eidsness, M.K., Kriauciunas, A., Frolik, C.A., and Chen, V.J. 1992. X-ray absorption spectroscopic studies of the high-spin iron(II) active site of isopenicillin N synthase: evidence for Fe-S interaction in the enzyme-substrate complex. Biochemistry 31:4596-4601.
   Google Scholar
• Sedgwick, B. and Lindahl, T. 2002. Recent progress on the Ada re-sponse for inducible repair of DNA alkylation damage. Oncogene 21:8886-8894.
   Google Scholar
• Senda, T., Sugiyama, K., Narita, H., Yamamoto, T., Kimbara, K., Fukuda, M., Sato, M., Yano, K., and Mitsui, Y. 1996. Three-dimensional structures of free form and two substrate complexes of an extradiol ring-cleavage type dioxygenase, the BphC enzyme from Pseudomonas sp. strain KKS102. J Mol Biol 255:735-752.
   Google Scholar
• Seo, J.-A., Proctor, R.H., and Plattner, R.D. 2001. Characterization of four clustered and coregulated genes associated with fumonisin biosynthesis in Fusarium verticillioides. Fungal Genet Biol 34:155-165.
   Google Scholar
• Serre, L., Sailland, A., Sy, D., Boudec, P., Rolland, A., Pebay-Peyroula, E., and Cohen-Addad, C. 1999. Crystal structure of Pseudomonas fluorescens 4-hydroxyphenylpyruvate dioxygenase: an enzyme involved in the tyrosine degradation pathway. Structure 7:977-988.
   Google Scholar
• Shaffer, P.M., Cairns, J.R., Dorman, D.C., and Lott, A.M. 1984. Separation and characterization of pyrimidine deoxyribonucleoside 2'-hydroxylase and thymine 7-hydroxylase from Aspergillus nidu-lans. Int J Biochem 16:429-434.
   Google Scholar
• Shaffer, P.M., McCroskey, R.P, Palmatier, R.D., Midgett, R.J., and Abbott, M.T. 1968. The cell-free conversion of a deoxyribonucle-oside to a ribonucleoside without detachment of the deoxyribose. Biochem Biophys Res Commun 33:806-811.
   Google Scholar
• Shaw, J.-F., Chou, Y-S., Chang, R.-C, and Yang, S.F. 1996. Characterization of the ferrous ion binding sites of apple 1-aminocyclopropane-1-carboxylate oxidase by site-directed mutagenesis. Biochem Biophys Res Commun 225:697-700.
   Google Scholar
• Shibasaki, T., Mori, H., Chiba, S., andOzaki, A. 1999. Microbialproline 4-hydroxylase screening and gene cloning. Appl Environ Microbiol 65:4028-4031.
   Google Scholar
• Simaan, A.J., Banse, F., Mialane, P., Boussac, A., Un, S., Kargar-Grisel, T., Bouchoux, G., and Girerd, JJ. 1999. Characterization of a non-heme mononuclear peroxoiron(III) intermediate by UV vis and EPR spectroscopy and mass spectrometry. EurJInorg Chem 6:993-999.
   Google Scholar
• Smith, JJ. and John, P. 1993. Activation of 1-aminocyclopropane-1carboxylate oxidase by bicarbonate/carbon dioxide. Phytochem 32:1381-1386.
   Google Scholar
• Solomon, E.I., Brunold, T.C., Davis, M.I., Kemsley, J.N., Lee, S.-K., Lehnert, N., Neese, F., Skulan, A.J., Yang, Y-S., and Zhou, J. 2000. Geometric and electronic structure/function correlations in non-heme iron enzymes. Chem Rev 100:235-349.
   Google Scholar
• Sono, M., Roach, M.P, Coulter, E.D., and Dawson, J.H. 1996. Heme-containing oxygenases. Chem Rev 96:2841-2887. Springob, K., Nakajima, J.I., Yamazaki, M., and Saito, K. 2003. Recent advances in the biosynthesis and accumulation of anthocyanins. Nat ProdRep 20:288-303.
   Google Scholar
• Stenflo, J., Holme, E., Lindstedt, S., Chandramouli, N., Huang, L.H.T., Tam, J.P, and Merrifield, R.B. 1989. Hydroxylation of aspartic acid Tryggvason, K., Risteli, J., and Kivirikko, K.I. 1976. Separation of prolyl 3-hydroxylase and 4-hydroxylase activities and the 4-hydroxyproline requirement for synthesis of 3-hydroxyproline. Biochem Biophys Res Commun 76:275-281.
   Google Scholar
• Tuderman, L., Myllyla, R., and Kivirikko, K.I. 1977. Mechanism of prolyl hydroxylase reaction. 1. Roleof co-substrates. Eur J Biochem 80:314-348.
   Google Scholar
• Turnbull, J.J., Nagle, M.J., Seibel, J.F., Welford, R.W.D., Grant, G.H., and Schofield, CJ. 2003. The C-4 stereochemistry of leucocyani-dine substrates for anthocyanidin synthase affects product selectivity. Bioorg Med Chem Lett 13:3853-3857.
   Google Scholar
• Turnbull, J.J., Nakajima, J.I., Welford, R.W., Yamazaki, M., Saito, K., and Schofield, CJ. 2004. Mechanistic studies on three 2-oxoglutarate dependent oxygenases of flavonoid biosynthesis: anthocyanidin synthase, flavonol synthase, and flavaonone 3b hydroxylase. JBiol Chem 279:1206-1216.
   Google Scholar
• Udenfriend, S. and Cardinale, G. 1982. a-Ketoglutarate-coupled dioxy-genases. In Oxygenases and Oxygen Metabolism, pp. 99-110, M. Nozaki, S. Yamamoto, Y. Ishimura, M.J. Coon, L. Ernster, and R.W. Estabrook, Eds., Academic Press, New York.
   Google Scholar
• Valegard, K., Terwisscha van Scheltinga, A.C., Dubus, A., Ranghino, G., Oster, L.M., Hajdu, J., and Andersson, I. 2004. The structural basis of cephalosporin formation in a mononuclear ferrous enzyme. Nat Struct Biol in press.
   Google Scholar
• Valegard, K., Terwisscha van Scheltinga, A.C., Lloyd, M.D., Hara, T., Ramaswamy, S., Perrakis, A., Thompson, A., Lee, W.-J., Baldwin, J.E., Schofield, C.J., Hajdu, J., and Andersson, I. 1998. Structure of a cephalosporin synthase. Nature (London) 394:805-809.
   Google Scholar
• Valtavaara, M., Papponen, H., Pirttila, A.M., Hiltunen, K., Helander, H., and Myllyla, R. 1997. Cloning and characterization of a novel human lysyl hydroxylase isoform highly expressed in pancreas and muscle. J Biol Chem 272:6831-6834.
   Google Scholar
• Valtavaara, M., Szpirer, C, Szpirer, J., and Myllyla, R. 1998. Pri-mary structure, tissue distribution, and chromosomal localization of a novel isoform of lysyl hydroxylase (lysyl hydroxylase 3). J Biol Chem 273:12881-12886.
   Google Scholar
• Vaz, F.M., Ofman, R., Westinga, K., Back, J.W., and Wanders, R.J.A. 2001. Molecular and biochemical characterization of rat N-trimethyllysine hydroxylase, the first enzyme of carnitine biosynthesis. J Biol Chem 276:33512-33517.
   Google Scholar
• Vaz, F.M., van Gool, S., Ofman, R., Ijlst, L., and Wanders, R.J.A. 1998. Carnitine biosynthesis: identification of the cDNA encoding human y -butyrobetaine hydroxylase. Biochem Biophys Res Commun 250:506-510.
   Google Scholar
• Vaz, F.M. and Wanders, R.J.A. 2002. Carnitine biosynthesis in mam-mals. Biochem J 361:417-429.
   Google Scholar
• Vazquez-Flota, F., De Carolis, E., Alarco, A.-M., and De Luca, V. 1997. Molecular cloning and characterization of desacetoxyvindoline-4-hydroxylase, a 2-oxoglutarate dependent-dioxygenase involved in the biosythesis of vindoline in Catharanthus roseus (L.) G. Don. Plant Molec Biol 34:935-948.
   Google Scholar
• Veijola, J., Koivunen, P., Annunem, P., Pihlajaniemi, T., and Kivirikko, K.I. 1994. Cloning, Baculovirus expression, and characterization of the a subunit of prolyl 4-hydroxylase from the nematode Caenorha-ditis elegans. This a subunit forms an active a/3 dimer with the human protein disulfide isomerase subunit. J Biol Chem 269:26746-26753.
   Google Scholar
• Verhoeven, N.M., Schor, D.S.M., ten Brink, H.J., Wanders, R.J.A., and Jakobs, C. 1997. Resolution of the phytanic acid a-oxidation path-way: identification of pristanal as product of the decarboxylation of 2-hydroxyphytanoyl-CoA. Biochem Biophys Res Commun 237:33-36.
   Google Scholar
• Wada, A., Ogo, S., Watanabe, Y, Mukai, M., Kitagawa, T., Jitsukawa, K., Masuda, H., and Einaga, H. 1999. Synthesis and characterization of novel alkylperoxo mononuclear iron(III) complexes with a tripodal pyridylamine ligand: a model for peroxo intermediates in reactions catalyzed by non-heme iron enzymes. Inorg Chem 38:3592-3593.
   Google Scholar
• Wang, Q., VanDusen, W.J., Petroski, C.J., Garsky, V.M., Stern, A.M., and Friedman, PA. 1991. Bovine liver aspartyl /3-hydroxylase. Purification and characterization. J Biol Chem 266:14004-14010.
   Google Scholar
• Warn-Cramer, B.J., Macrander, L.A., and Abbott, M.T. 1983. Markedly different ascorbate dependencies of the sequential a-ketoglutarate dioxygenase reactions catalyzed by an essentially homogeneous thymine 7-hydroxylase from Rhodotorula glutinis. J Biol Chem 258:10551-10557.
   Google Scholar
• Watanabe, M., Sumida, N., Murakami, S., Anzai, H., Thompson, C.J., Tateno, Y, and Murakami, T. 1999. A phosphonate-induced gene which promotes Penicillium-mediated bioconversion of cis-propenylphosphonic acid to fosfomycin. Appl Environ Microbiol 65:1036-1044.
   Google Scholar
• Watkins, P.A., Howard, A.E., and Mihalik, S.J. 1994. Phytanic acid must be activated to phytanoyl-CoA prior to its a-oxidation in rat liver peroxisomes. Biochim Biophys Acta 1214:288-294.
   Google Scholar
• Wei, Y.-F., Carter, K.C., Wang, R.-P, and Shell, B.K. 1996. Molecular cloning and functional analysis of a human cDNA encoding an Es-cherichia coli AlkB homolog, a protein involved in DNA alkylation damage repair. Nucl Acids Res 24:931-937.
   Google Scholar
• Welford, R.W.D., Schlemminger, I., McNeill, L.A., Hewitson, K.S., and Schofield, CJ. 2003. The selectivity and inhibition of AlkB. J Biol Chem 278:10157-10161.
   Google Scholar
• Wellman, F., Lukacin, R., Moriguchi, T., Britsch, L., Schiltz, E., and Matern, U. 2002. Functional expression and mutational analysis of flavonol synthase from Citrus unshiu. Eur J Biochem. 269:4134-4142.
   Google Scholar
• Wellman, F., Matern, U., and Lukacin, R. 2004. Significance of C-terminal sequence elements for Petunia flavanone 3/3-hydroxylase activity. FEBS Lett 561:149-154.
   Google Scholar
• Westendorf, A., Muller, A., and Babel, W. 2003. Purification and characterization of the enantiospecific dioxygenases from Delftia acidovorans MC1 initiating the degradation of phenoxypropionate and phenoxyacetate herbicides. Acta Biotechnol 23:3-17.
   Google Scholar
• White, A.K. and Metcalf, W.W. 2002. Isolation and biochemical char-acterization of hypophosphite/2-oxoglutarate dioxygenase. A novel phosphorus-oxidizing enzyme from Pseudomonas stutzeri WM88. J Biol Chem 277:38262-38271.
   Google Scholar
• Whiting, A.K., Que, L., Jr., Saari, R.E., Hausinger, R.P, Fredrick, M.A., and McCracken, J. 1997. Metal coordination environment of a Cu(II)-substituted a-keto acid-dependent dioxygenase that de-grades the herbicide 2,4-D. J Am Chem Soc 119:3413-3414.
   Google Scholar
• Wierzbicki, A.S., Lloyd, M.D., Schofield, C.J., Feher, M.D., and Gibberd, FB. 2002. Refsum's disease: a peroxisomal disor-der affecting phytanic acid a-oxidation. J Neurochem 80:727-735.
   Google Scholar
• Wilmouth, R.C., Turnbull, J.J., Welford, R.W.D., Clifton, I.J., Prescott, A.G., and Schofield, CJ. 2002. Structure and mechanism of anthocyanidin synthase from Arabidopsis thaliana. Structure 10:93- 103.
   Google Scholar
• Wu, H., de Graaf, B., Mariani, C., and Cheung, A.Y. 2001. Hydroxyproline-rich glycoproteins in plant reproductive tissues: structure, functions and regulation. Cell Molec Life Sci 58:1418- 1429.
   Google Scholar
• Yin, X., O'Hare, T., Gould, S.J., and Zabriskie, T.M. 2003. Identifi-cation and cloning of genes encoding viomycin biosynthesis from Streptomyces vinaceus and evidence for involvement of a rare oxy-genase. Gene 312:215-224.
   Google Scholar
• Zhang, J.H., Quigley, N.B., and Gross, D.C. 1995. Analysis of syrB and syrC genes of Pseudomonas syringae pv. syringae indicates that syringomycin is synthesized by a template mechanism. J Bacteriol 177:4009-4020.
   Google Scholar
• Zhang, Z., Barlow, J.N., Baldwin, J.E., and Schofield, C.J. 1997. Metal-catalyzed oxidation and mutagenesis studies on the iron(II) binding site of 1-aminocyclopropane-1-carboxylate oxidase. Biochemistry 36:15999-16007.
   Google Scholar
• Zhang, Z., Ren, J., Stammers, D.K., Baldwin, J.E., Harlos, K., and Schofield, C.J. 2000. Structural origins of the selectivity of the trifunctional oxygenase clavaminic acid synthase. Nat Struct Biol 7:127-133.
   Google Scholar
• Zhang, Z., Ren, J.-S., Harlos, K., McKinnon, C.H., Clifton, I.J., and Schofield, C.J. 2002. Crystal structure of a clavaminate synthase-Fe(II)-2-oxoglutarate-substrate-NO complex: evidence for metal centred rearrangements. FEBS Lett 517:7-12.
   Google Scholar
• Zhou, J., Gunsior, M., Bachmann, B.O., Townsend, C.A., and Solomon, E.I. 1998. Substrate binding to the -ketoglutarate-dependent non-heme iron enzyme clavaminate synthase 2: coupling mechanism of oxidative decarboxylation and hydroxylation. J Am Chem Soc 120:13539-13540.
   Google Scholar
• Zhou, J., Rocklin, A.M., Lipscomb, J.D., Que, L., Jr., and Solomon, E.I. 2002. Spectroscopic studies of 1-aminocyclopropane-1-carboxylic acid oxidase: molecular mechanism andCO2 activationinthe biosyn-thesis of ethylene. J Am Chem Soc 124:4602-4609.
   Google Scholar
• Zhou, J., Kelly, W.L., Bachmann, B.O., Gunsior, M., Townsend, C.A., and Solomon, E.I. 2001. Spectroscopic studies of substrate interactions with clavaminate synthase 2, a multifunctional KG-dependent non-heme iron enzyme: correlation with mechanisms and reactivities. J Am Chem Soc 123:7388-7398.
   Google Scholar