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Expert Opinion on Therapeutic Targets Volume 7, 2003 - Issue 3
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Review

Secreted phospholipase A2 enzymes as therapeutic targets

Kieran F Scott St Vincent's Hospital Clinical School, The University of New South Wales, Level 7 Garvan Building, 384 Victoria Street, Sydney, NSW 2010, Australia. [email protected]
,
Garry G Graham St Vincent's Hospital Clinical School, The University of New South Wales, Level 7 Garvan Building, 384 Victoria Street, Sydney, NSW 2010, Australia. [email protected]
&
Katherine J Bryant St Vincent's Hospital Clinical School, The University of New South Wales, Level 7 Garvan Building, 384 Victoria Street, Sydney, NSW 2010, Australia. [email protected]
Pages 427-440 | Published online: 02 Mar 2005

Bibliography

  • SIX DA, DENNIS EA: The expanding superfamily of phospholipase A2 enzymes: classification and characterization. Bloch/m. Biophys. Acta (2000) 1488:1–19.
  • MURAKAMI M, KUDO I: Phospholipase A2. I Biochem. (2002) 131:285–292.
  • •Recent review of PLA2 structure and function.
  • VADAS P, WASI S, MOVAT HZ, HAY JB: Extracellular phospholipase A2 mediates inflammatory hyperemia. Nature (1981) 293:583–585.
  • ••Original report of sPLA2 pro-inflammatoryactivity in vivo.
  • UOZUMI N, KUME K, NAGASE T et al.: Role of cytosolic phospholipase A2 in allergic response and parturition. Nature (1997) 390:618–622.
  • BONVENTRE JV, HUANG Z, TAHERI MR et al: Reduced fertility and postischaemic brain injury in mice deficient in cytosolic phospholipase A2. Nature (1997) 390:622–625.
  • WONG DA, KITA Y, UOZUMI N, SHIMIZU T: Discrete role for cytosolic phospholipase A2-a in platelets: studies using single and double mutant mice of cytosolic and Group IIA secretory phospholipase A2. j. Exp. Med. (2002) 196:349–357.
  • LEHR M: Phospholipase A2 inhibitors in inflammation. Expert Opin. Ther. Patents (2001) 11:1123–1136.
  • JENKINS CM, HAN X, MANCUSO DJ, GROSS RW: Identification of calcium-independent phospholipase A2 (iPLA2)-(3, and not iPLA2-y, as the mediator of arginine vasopressin-induced arachidonic acid release in A-10 smooth muscle cells. Enantioselective mechanism-based discrimination of mammalian iPLA2s. J. Biol. Chem. (2002) 277:32807–32814.
  • GUO Z, SU W, MA Z, SMITH GM, GONG MC: Ca2+-independent phospholipase A2 is required for agonist-induced Ca2±-sensitization of contraction in vascular smooth muscle. Biol. Chem. (2002) 278:1856–1863.
  • SUCKLING KE, MACPHEE CH: Lipoprotein-associated phospholipase A2: a target directed at the atherosclerotic plaque. Expert Opin. Ther. Targets (2002) 6:309–314.
  • DADA N, KIM NW, WOLFERT RL: Lp-PLA2: an emerging biomarker of coronary heart disease. Expert Rev Mol. Diagn. (2002) 2:17–22.
  • CHEN J, ENGLE S, SEILHAMER J, TISCHFIELD J: Cloning and characterization of novel rat and mouse low molecular weight Ca(2F)dependent phospholipase A2s containing 16 cysteines. J. Biol. Chem. (1994) 269:23018–23024.
  • TISCHFIELD JA, XIA YR, SHIH DM et al: Low molecular weight, calcium-dependent phospholipase A2 genes are linked and map to homologous chromosome regions in mouse and humans. Cenomics (1996) 32:328–333.
  • CUPILLARD L, KOUMANOV K, MATTEI MG, LAZDUNSKI M, LAMBEAU G: Cloning, chromosomal mapping, and expression of a novel human secretory phospholipase A2. J. Biol. Chem. (1997) 272:15745–15752.
  • GELB MH, VALENTIN E, GHOMASHCHI F, LAZDUNSKI M, LAMBEAU G: Cloning and recombinant expression of a structurally novel human secreted phospholipase A2. I. Biol. Chem. (2000) 275:39823–39826.
  • HO IC, ARM JP, BINGHAM CO III, CHOI A, AUSTEN KF, GLIMCHER LH: A novel group of phospholipase A2s preferentially expressed in Type 2 helper T cells. J. Biol. Chem. (2001) 276:18321–18326.
  • VALENTIN E, GHOMASHCHI F, GELB MH, LAZDUNSKI M, LAMBEAU G: Novel human secreted phospholipase A2 with homology to the Group III bee venom enzyme. J. Biol. Chem. (2000) 275:7492–7496.
  • SEILHAMER JJ, RANDALL TL, YAMANAKA M, JOHNSON LK: Pancreatic phospholipase A2: isolation of the human gene and cDNAs from porcine pancreas and human lung. DNA (1986) 5:519–527.
  • KRAMER R, HESSION C, JOHANSEN B et al: Structure and properties of a human non-pancreatic phospholipase A2. J. Biol. Chem. (1989) 264:5768–5775.
  • SEILHAMER J, PRUZANSKI W, VADAS P et al.: Cloning and recombinant expression of phospholipase A2 present in rheumatoid arthritic synovial fluid. J. Biol. Chem. (1989) 264:5335–5338.
  • GREEN JA, SMITH GM, BUCHTA R et al.: Circulating phospholipase A2 activity associated with sepsis and septic shock is indistinguishable from that associated with rheumatoid arthritis. Inflammation (1991) 15:355–367.
  • SMITH GM, WARD RL, MCGUIGAN L, RAJKOVIC IA, SCOTT KF: Measurement of human phospholipase A2 in arthritis plasma using a newly developed sandwich ELISA. BE J. Rheumatol (1992) 31:175–178.
  • GRONROOS JM, NEVALAINEN TJ: Increased concentrations of synovial-type phospholipase A2 in serum and pulmonary and renal complications in acute pancreatitis. Digestion (1992) 52:232–236.
  • LIN MKS, FAREWELL V, VADAS P, BOOKMAN AAS, KEYSTONE EC, PRUZANSKI W: Secretory phospholipase A2 as an index of disease activity in rheumatoid arthritis. Prospective double-blind study of 212 patients. Rheumatol (1996) 23:1162.
  • RICHMOND BL, BOILEAU AC, ZHENG S et al: Compensatory phospholipid digestion is required for cholesterol absorption in pancreatic phospholipase A2-deficient mice. Gastroenterology (2001) 120:1193–1202.
  • HUGGINS KW, BOILEAU AC, HUI DY: Protection against diet-induced obesity and obesity-related insulin resistance in Group IB PLA2-deficient mice. Am. J. Physiol Endocrinol Metab. (2002) 283:E994–E1001.
  • NEVALAINEN TJ: Serum phospholipase A2 in inflammatory disease. Clin. Chem. (1993) 39:2453–2549.
  • ANCIAN P, LAMBEAU G, MATTEI MG, LAZDUNSKI M: The human 180 kDa receptor for secretory phospholipases A2. J. Biol. Chem. (1995) 270:8963–8970.
  • HANASAKI K, ARITA H: Phospholipase A2 receptor: a regulator of biological functions of secretory phospholipase A2. Prostaglandins Other Lipid Medial-. (2002) 68–69:71–82.
  • HANASAKI K, ARITA H: Biological andpathological functions of phospholipase A2 receptor. Arch. Biochem. Biophys. (1999) 372:215–223.
  • HANASAKI K, YOKOTA Y, ISHIZAKI J,ITOH T, ARITA H: Resistance to endotoxic shock in phospholipase A2 receptor-deficient mice. J. Biol. Chem. (1997) 272:32792–32797.
  • •Evidence for an in vivo role of the sPLA2 receptor in pathology.
  • YOKOTA Y, HANASAKI K, ONO T, NAKAZATO H, KOBAYASHI T, ARITA H: Suppression of murine endotoxic shock by sPLA2 inhibitor, indoxam, through Group IIA sPLA2-independent mechanisms. Biochim. Biophys. Acta (1999) 1438:213–222.
  • TIBES U, FRIEBE W: Phospholipase A2 inhibitors in development. Expert Opin. Invest. Drugs (1997) 6:279–298.
  • MAYER RJ, MARSHALL LA: The therapeutic potential for phospholipase A2 inhibitors. Expert Opin. Emerg. Drugs (1998) 3:333–344.
  • SPRINGER DM: An update on inhibitors of human 14 kDa Type II s-PLA2 in development. Curr. Pharm. Des. (2001) 7:181–198.
  • •Review of sPLA2 drug development progress.
  • NEVALAINEN TJ, HAAPAMAKI MM, GRONROOS JM: Role of secretory phospholipases A2 in inflammatory diseases and trauma. Biochim. Biophys. Acta (2000) 1488:83–90.
  • •Review of sPLA2 in inflammation.
  • HUHTINEN HT, GRONROOS JM, HAAPAMAKI MM, NEVALAINEN TJ: Source of Group II phospholipase A2 in gastric juice. Scand. I Clin. Lab. Invest. (2002) 62:123–128.
  • LAINE VJO, GRASS DS, NEVALAINEN TJ: Protection by Group II phospholipase A2 against Staphylococcus aureus. j Immunol (1999) 162:7402–7408.
  • LAINE VJO, GRASS DS, NEVALAINEN TJ: Resistance of transgenic mice expressing human Group II phospholipase A2 to Escherichia cob infection. Infect. Immun. (2000) 68:87–92.
  • BOWTON DL, SEEDS MC, FASANO MB, GOLDSMITH B, BASS DA: Phospholipase A2 and arachidonate increase in bronchoalveolar lavage fluid after inhaled antigen challenge in asthmatics. Am. I Respir: Crit. Care Med. (1997) 155:421–425.
  • KIM DK, FUKUDA T, THOMPSON BT, COCKRILL B, HALES C, BONVENTRE JV: Broncheoalveolar lavage fluid phospholipase A2 activities are increased in human adult respiratory distress syndrome. Am. I Physiol Lung Cell Mol. Physiol (1995) 269:L109–L118.
  • MINAMI T, TOJO H, SHINOMURA Y, MATSUZAWA Y, OKAMOTO M: Increased Group II phospholipase A2 in colonic mucosa of patients with Crohn's disease and ulcerative colitis. Gut (1994) 35:1593–1598.
  • LASHNER B, KORZENIK J, DMITRIENKO A, HUNT R, MYERS S, KRUEGER K: Safety and efficacy of an sPLA2 inhibitor in treating ulcerative colitis. Am. J. Gastroenterof (2001) 96\(Suppl. 1):5297.
  • YOSHIKAWA T, NARUSE S, KITIGAWA M et al.: Effect of a new inhibitor of Type II phospholipase A2 on experimental acute pancreatitis in rats. Pancreas (1999) 19:193–198.
  • KOIKE K, YAMAMOTO Y, HORT Y, ONO T: Group IIA phospholipase A2 mediates lung injury in intestinal ischemia-reperfusion. Ann. Surg. (2000) 232:90–97.
  • FURUE S, KUWABARA K, KATSUYA M et al.: Crucial role of Group IIA phospholipase A2 in oleic acid-induced acute lung injury in rabbits. Am. I Respir. Crit. Care Med. (1999) 160:1292–1302.
  • FURUE S, MIKAWA K, NISHINA K et al:Therapeutic time-window of a Group IIA phospholipase A2 inhibitor in rabbit acute lung injury: correlation with lung surfactant protection. Crit. Care Med. (2001) 29:719–727.
  • IVANDIC B, CASTELLANI LW, WANG XP et al: Role of Group II secretory phospholipase A2 in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. (1999) 19:1284–1290.
  • HURT-CAMEJO E, CAMEJO G, PEILOT H, OORNI K, KOVANEN P: Phospholipase A2 in vascular disease. Circ. Res. (2001) 89:298–304.
  • •Review of sPLA2 in atherosclerosis.
  • OGATA K, JIN MB, TANIGUCHI M et al.: Attenuation of ischemia and reperfusion injury of canine livers by inhibition of Type II phospholipase A2 with LY-329722. Transplantation (2001) 71:1040–1046.
  • FORD DA: Alterations in myocardial lipid metabolism during myocardial ischemia and reperfusion. Prog. Lipid Res. (2002) 41:6–26.
  • GRAFF JR, KONICEK BW, DEDDENS JA et al.: Expression of Group IIa secretory phospholipase A2 increases with prostate tumor grade. Clin. Cancer Res. (2001) 7:3857–3861.
  • JIANG J, NEUBAUER BL, GRAFF JR et al.: Expression of Group IIA secretory phospholipase A2 is elevated in prostatic intraepithelial neoplasia and adenocarcinoma. Am. I Pathol (2002) 160:667–671.
  • LIU XH, KIRSCHENBAUM A, YAO S, LEE R, HOLLAND JF, LEVINE AC: Inhibition of cyclooxygenase-2 suppresses angiogenesis and the growth of prostate cancer IP vivo. J. Urol. (2000) 164:820–825.
  • KELAVKAR UP, NIXON JB, COHEN C, DILLEHAY D, ELING TE, BADR KF: Overexpression of 15-lipoxygenase-1 in PC-3 human prostate cancer cells increases tumorigenesis. Carcinogenesis (2001) 22: 1765-1773.
  • NWOSU V, CARPTEN J, TRENT JM, SHERIDAN R: Heterogeneity of genetic alterations in prostate cancer: evidence of the complex nature of the disease. Hum. Mol. Genet. (2001) 10:2313–2318.
  • CORNELIS F, FAURE S, MARTINEZ M et al.: New susceptibility locus for rheumatoid arthritis suggested by a genome-wide linkage study. Proc. Natl. Acad. ScL USA (1998) 95:10746–10750.
  • BECKER KG, SIMON RM, BAILEY-WILSON JE et al.: Clustering of non-major histocompatibility complex susceptibility candidate loci in human autoimmune diseases. Proc. Natl. Acad. Sci. USA (1998) 95:9979–9984.
  • MACPHEE M, CHEPENICK KP, LIDDELL RA, NELSON KK, SIRACUSA LD, BUCHBERG AM: The secretory phospholipase A2 gene is a candidate for the Mom 1 locus, a major modifier of APCAI'Linduced intestinal neoplasia. Cell (1995) 81:957–966.
  • CORMIER RT, HONG KH, HALBERG RB et al.: Secretory phospholipase Pla2g2a confers resistance to intestinal tumorigenesis. Nat. Genet. (1999) 17:88–91.
  • PRAML C, AMLER LC, DIHLMANN S, FINKE LH, SCHLAG P, SCHWAB M: Secretory Type II phospholipase A2 (PLA2G2A) expression status in colorectal carcinoma derived cell lines and in normal colonic mucosa. Oncogene (1998) 17: 2009-2012.
  • THORSTENSEN L, OVIST H, HEIM S et al.: Evaluation of lp losses in primary carcinomas, local recurrences and peripheral metastases from colorectal cancer patients. Neoplasia (2000) 2:514–522.
  • LEUNG SY, CHEN X, CHU KM et al: Phospholipase A2 Group IIA expression in gastric adenocarcinoma is associated with prolonged survival and less frequent metastasis. Proc. Natl. Acad. Li. USA (2002) 99:16203–16208.
  • CHEN J, ENGLE S, SEILHAMER J, TISCHFIELD J: Cloning and recombinant expression of a novel human low molecular weight Ca(2±)-dependent phospholipase A2. Biol. Chem. (1994) 269:2365–2368.
  • CHO W: Structure, function and regulation of Group V phospholipase A2. Biochim. Biophys. Acta (2000) 1488:48–58.
  • •Review of sPLA2–V.
  • SCOTT KF, BRYANT KJ, BID GOOD MJ: Functional coupling and differential regulation of phospholipase A2-cyclooxygenase pathways in inflammation. J. Leukocyte Biol. (1999) 66:535–541.
  • MUNOZ NM, BOETTICHER E, SPERLING E et al.: Quantitation of secretory Group V phospholipase A2 in human tissues by sandwich enzyme-linked immunosorbent assay. Immunol. Methods (2002) 262:41–51.
  • KENNEDY BP, PAYETTE P, MUDGETT J et A natural disruption of the secretory Group II phospholipase A2 in inbred mouse strains. J. Biol. Chem. (1995) 270:22378–22385.
  • •Identification of genetic variation in expression of sPLA2-IIA in mice.
  • SAWADA H, MURAKAMI M, ENOMOTO A, SHIMBARA S, KUDO I: Regulation of Type V phospholipase A2 expression and function by proinflammatory stimuli. Eur..1. Biochem. (1999) 263:826–833.
  • •Variation in expression of sPLA2 forms between species.
  • KIM YJ, KIM KP, HAN SK et al: Group V phospholipase A2 induces leukotriene biosynthesis in human neutrophils through the activation of Group IVA phospholipase A2. Biol. Chem. (2002) 277:36479–36488.
  • DEGOUSEE N, GHOMASHCHI F, STEFANSKI E et al.: Groups IV, V, and X phospholipases A2s in human neutrophils. Role in eicosanoid production and Gram-negative bacterial phospholipid hydrolysis. J. Biol. Chem. (2002) 277:5061–5073.
  • GESQUIRE L, CHO W, SUBBAIAH PJ: Role of Group IIa and Group V secretory phospholipase A2 in the metabolism of lipoproteins. Substrate specificities of the enzymes and the regulation of their activities by sphingomyelin. Biochemistry (2002) 41:4911–4920.
  • GRONROOS JO, LAINE VJO, JANSSEN MJW, EGMOND MR, NEVALAINEN TJ: Bactericidal properties of Group IIA and Group V phospholipases A2. J. Immunol (2001) 166:4029–4034.
  • HANASAKI K, ONO T, SAIGA A et al: Purified Group X secretory phospholipase A2 induced prominent release of arachidonic acid from human myeloid leukemia cells. Biol Chem. (1999) 274:34203–34211.
  • BEZZINE S, KODURI RS, VALENTIN E et al.: Exogenously added human Group X secreted phospholipase A2 but not the Group IB, IIA, and V enzymes efficiently release arachidonic acid from adherent mammalian cells. Biol. Chem. (2000) 275:3179–3191.
  • SINGER AG, GHOMASHCHI F, LE CALVEZ C et al: Interfacial kinetic and binding properties of the complete set of human and mouse Groups I, II, V, X, and XII secreted phospholipases A2. J. Biol. Chem. (2002) 277:48535–48549.
  • •Comparative analysis of functional properties of and the effect of inhibitors on known human and mouse sPLA2 enzymes.
  • KODURI RS, GRONROOS JO, LAINE VJO et al: Bactericidal properties of human and murine Groups I, II, V, X, and XII secreted phospholipases A2. j Biol. Chem. (2002) 277:5849–5857.
  • SEEDS MC, JONES KA, DUNCAN HITE R et Cell-specific expression of Group X and Group V secretory phospholipases A2 in human lung airway epithelial cells. Am. J. Respic Cell Mol. Biol. (2000) 23:37–44.
  • MORIOKA Y, IKEDA M, SAIGA A et al.: Potential role of Group X secretory phospholipase A2 in cyclooxygenase-2-dependent PGE2 formation during colon carcinogenesis. FEBS Lett. (2000) 487:262–266.
  • OSTERSTROM A, DIMBERG J, FRANSEN K, SODERKVIST P: Expression of cytosolic and Group X phospholipase A2 in human colorectal adenocarcinoma. Cancer Lett. (2002) 182:175–182.
  • HANASAKI K, YAMADA K, YAMAMOTO S et al: Potent modification of low density lipoprotein by Group X secretory phospholipase A2 is linked to macrophage foam cell formation. Biol Chem. (2002) 277:29116–29124.
  • ISHIZAKI J, SUZUKI N, HIGASHINO K-I et al: Cloning and characterization of novel mouse and human secretory phospholipase A2s. I Biol. Chem. (1999) 274:24973–24979.
  • MURAKAMI M, YOSHIHARA K, SHIMBARA S et al.: Group IID heparin-binding secretory phospholipase A2 is expressed in human colon carcinoma cells and human mast cells and upregulated in mouse inflammatory tissues. Eur..1. Biochem. (2002) 269:2698–2707.
  • JAMAL OS, CONAGHAN PG, CUNNINGHAM AM, BROOKS PM, MUNRO VF, SCOTT KF: Increased expression of human Type Ha secretory phospholipase A2 antigen in arthritic synovium. Ann. Rheum. Dis. (1998) 57:550–558.
  • LILJA I, GUSTAFSON-SVARD C, FRANZEN L, SJODAHL R, ANDERSEN S, JOHANSEN B: Presence of Group IIa secretory phospholipase A2 in mast cells and macrophages in normal human ileal submucosa and in Crohn's disease. Clim Chem. Lab. Med. (2000) 38:1231–1236.
  • SUZUKI N, ISHIZAKI J, YOKOTA Y et al.: Structures, enzymatic properties, and expression of novel human and mouse secretory phospholipase A2s. I Biol. Chem. (2000) 275:5785–5793.
  • MURAKAMI M, YOSHIHARA K, SHIMBARA S et al: Arachidonate release and eicosanoid generation by Group IIE phospholipase A2. Biochem. Biophys. Res. Comm. (2002) 292:689–696.
  • VALENTIN E, GHOMASHCHI F, GELB MH, LAZDUNSKI M, LAMBEAU G: On the diversity of secreted phospholipases A2. Cloning, tissue distribution and functional expression of two novel mouse Group II enzymes. Biol Chem. (1999) 274:31195–31202.
  • MURAKAMI M, YOSHIHARA K, SHIMBARA S et al.: Cellular arachidonate-releasing function and inflammation associated expression of Group IIF secretory phospholipase A2. J. Biol. Chem. (2002) 277:19145–19155.
  • GILBERT J, STEWART A, COURTNEY C et al: Antigen receptors on immature, but not mature, B and T cells are coupled to cytosolic phospholipase A2 activation: expression and activation of cytosolic phospholipase A2 correlate with lymphocyte maturation. Immunol (1996) 156:2054–2061.
  • SCOTT DL, WHITE SP, BROWNING JL, ROSA JJ, GELB MH, SIGLER PB: Structures of free and inhibited human secretory phospholipase A2 from inflammatory exudate. Science (1991) 254:1007–1010.
  • WERY JP, SCHEVITZ RW, CLAWSON DK et al: Structure of recombinant human rheumatoid arthritic synovial fluid phospholipase A2 at 2.2A resolution. Nature (1991) 352:79–82.
  • PAN YH, YU B-Z, SINGER AG et al.: Crystal structure of human Group X secreted phospholipase A2. Electrostatically neutral interfacial binding surface targets zwitterionic membranes. J. Biol. Chem. (2002) 277:29086–29093.
  • SCHEVITZ RW, BACH DG, CARLSON NY et al.: Structure-based design of the first potent and selective inhibitor of human non-pancreatic secretory phospholipase A2. Nature Struct. Biol. (1995) 2:458–465.
  • ••First description of a structure-basedselective sPLA2 inhibitor.
  • CHURCH WB, INGLIS AS, TSENG A et al: A novel approach to the design of inhibitors of human secreted phospholipase A2 based on native peptide inhibition. .1. Biol. Chem. (2001) 276:33156–33164.
  • BIDGOOD MJ, JAMAL OS, CUNNINGHAM AM, BROOKS PM, SCOTT KF: Type IIA secretory phospholipase A2 up-regulates cyclooxygenase-2 and amplifies cytokine-mediated prostaglandin production in human rheumatoid synoviocytes. Immunol (2000) 165:2790–2797.
  • HERNANDEZ M, FUENTES L, JAVIER F, AVILES F, CRESPO MS, NIETO ML: Secretory phospholipase A2 elicits proinflammatory changes and upregulates the surface expression of Fas ligand in monocyte cells. Potential relevance to atherogenesis. Circ. Res. (2002) 90:38–45.
  • TRIGGIANI M, GRANATA F, ORIENTE A et al.: Secretory phospholipases A2 induce P-glucuronidase release and IL-6 production from human lung macrophages. j Immunol (2000) 164:4908–4915.
  • TRIGGIANI M, FRANCESCOPAOLO G, ORIENTE A et al.: Secretory phospholipase A2 induces cytokine release from blood and synovial fluid monocytes. Eur. Immunol. (2002) 32:67–76.
  • FOURCADE 0, SIMON MF, VIODE C et al.: Secretory phospholipase A2 generates the novel lipid mediator lysophosphatidic acid in membrane microvesicles shed from activated cells. Cell (1995) 80:919–927.
  • RENETSEDER R, BRUNIE S, DIJKSTRA B, DRENTH J, SIGLER P: A comparison of the crystal structures of phospholipase A2 from bovine pancreas and Crotalus atrox venom. Biol. Chem. (1985) 260:11627–11634.

Websites

  • http://www.ncbi.nlm.nih.gov Unigene database.
  • http://www.shionogi.cmjp/contents_e/ investors/annuaYannual-set.htm Shionogi Annual Report 2002, `a1102.pdf' p. 10.

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