Identification of Novel GTP Analogs as Potent and Specific Reversible Inhibitors for Transglutaminase 2

References

• Keillor JW, Apperley KY, Akbar A. Inhibitors of tissue transglutaminase. Trends Pharmacol Sci. 2015 Jan;36(1):32–40.
   PubMed Web of Science ®Google Scholar
• Griffin M, Casadio R, Bergamini CM. Transglutaminases: nature's biological glues. Biochem J. 2002 Dec 1;368(Pt 2):377–396.
   PubMedGoogle Scholar
• Huang L, Haylor JL, Hau Z, et al. Transglutaminase inhibition ameliorates experimental diabetic nephropathy. Kidney Int. 2009 Aug;76(4):383–394.
   PubMed Web of Science ®Google Scholar
• Fesus L, Piacentini M. Transglutaminase 2: an enigmatic enzyme with diverse functions. Trends Biochem Sci. 2002 Oct;27(10):534–539.
   PubMed Web of Science ®Google Scholar
• Di Venere A, Rossi A, De Matteis F, et al. Opposite effects of Ca(2+) and GTP binding on tissue transglutaminase tertiary structure. J Biol Chem. 2000 Feb 11;275(6):3915–3921.
   PubMed Web of Science ®Google Scholar
• Eckert RL, Kaartinen MT, Nurminskaya M, et al. Transglutaminase regulation of cell function. Physiol Rev. 2014 Apr;94(2):383–417.
   PubMed Web of Science ®Google Scholar
• Liu S, Cerione RA, Clardy J. Structural basis for the guanine nucleotide-binding activity of tissue transglutaminase and its regulation of transamidation activity. Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2743–2747.
   PubMed Web of Science ®Google Scholar
• Pinkas DM, Strop P, Brunger AT, et al. Transglutaminase 2 undergoes a large conformational change upon activation. PLoS Biology. 2007 Dec;5(12):e327.
   PubMed Web of Science ®Google Scholar
• Siegel M, Khosla C. Transglutaminase 2 inhibitors and their therapeutic role in disease states. Pharmacol Ther. 2007 Aug;115(2):232–245.
   PubMed Web of Science ®Google Scholar
• de Cristofaro T, Affaitati A, Cariello L, et al. The length of polyglutamine tract, its level of expression, the rate of degradation, and the transglutaminase activity influence the formation of intracellular aggregates. Biochem Biophys Res Commun. 1999 Jun 24;260(1):150–158.
   PubMed Web of Science ®Google Scholar
• Junn E, Ronchetti RD, Quezado MM, et al. Tissue transglutaminase-induced aggregation of alpha-synuclein: implications for Lewy body formation in Parkinson's disease and dementia with Lewy bodies. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):2047–2052.
   PubMed Web of Science ®Google Scholar
• Fok JY, Ekmekcioglu S, Mehta K. Implications of tissue transglutaminase expression in malignant melanoma. Mol Cancer Ther. 2006 Jun;5(6):1493–1503.
   PubMed Web of Science ®Google Scholar
• Verma A, Wang H, Manavathi B, et al. Increased expression of tissue transglutaminase in pancreatic ductal adenocarcinoma and its implications in drug resistance and metastasis. Cancer Res. 2006 Nov 1;66(21):10525–10533.
   PubMed Web of Science ®Google Scholar
• Yuan L, Siegel M, Choi K, et al. Transglutaminase 2 inhibitor, KCC009, disrupts fibronectin assembly in the extracellular matrix and sensitizes orthotopic glioblastomas to chemotherapy. Oncogene. 2007 Apr 19;26(18):2563–2573.
   PubMed Web of Science ®Google Scholar
• Freund KF, Doshi KP, Gaul SL, et al. Transglutaminase inhibition by 2-[(2-oxopropyl)thio]imidazolium derivatives: mechanism of factor XIIIa inactivation. Biochemistry. 1994 Aug 23;33(33):10109–10119.
   PubMed Web of Science ®Google Scholar
• Keillor JW, Chabot N, Roy I, et al. Irreversible inhibitors of tissue transglutaminase. Adv Enzymol Relat Areas Mol Biol. 2011 Oct;78:415–447.
   PubMedGoogle Scholar
• Datta S, Antonyak MA, Cerione RA. Importance of Ca(2+)-dependent transamidation activity in the protection afforded by tissue transglutaminase against doxorubicin-induced apoptosis. Biochemistry. 2006 Nov 7;45(44):13163–13174.
   PubMed Web of Science ®Google Scholar
• Day N, Keillor JW. A continuous spectrophotometric linked enzyme assay for transglutaminase activity. Anal Biochem. 1999 Oct 1;274(1):141–144.
   PubMed Web of Science ®Google Scholar
• Kim S, Chen J, Cheng T, et al. Pubchem in 2021: new data content and improved web interfaces. Nucleic Acids Res. 2021 Jan 8;49(D1):D1388–D1395.
   PubMed Web of Science ®Google Scholar
• Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017 Mar 3;7:42717.
   PubMed Web of Science ®Google Scholar
• Lipinski CA. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol. 2004 Dec;1(4):337–341.
   PubMedGoogle Scholar
• Schyman P, Liu R, Desai V, et al. vNN Web server for ADMET predictions. Front Pharm. 2017 Dec;8:889.
   PubMed Web of Science ®Google Scholar
• Guex N, Peitsch MC. SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis. 1997 Dec;18(15):2714–2723.
   PubMed Web of Science ®Google Scholar
• Trott O, Olson AJ. Autodock vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010 Jan 30;31(2):455–461.
   PubMed Web of Science ®Google Scholar
• Schrödinger L. DW. The PyMOL Molecular Graphics System. 2002.
   Google Scholar
• Pronk S, Pall S, Schulz R, et al. GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics. 2013 Apr 1;29(7):845–854.
   PubMed Web of Science ®Google Scholar
• Hess B. P-LINCS: A parallel linear constraint solver for molecular simulation. J Chem Theory Comput. 2008 Jan;4(1):116–122.
   PubMed Web of Science ®Google Scholar
• Vanommeslaeghe K, Hatcher E, Acharya C, et al. CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. J Comput Chem. 2010 Mar;31(4):671–690.
   PubMed Web of Science ®Google Scholar
• Darden TA, York DM, Pedersen LG. Particle mesh ewald: An N⋅log(N) method for ewald sums in large systems. J Chem Phys. 1993 Aug;98:10089–10092.
   Web of Science ®Google Scholar
• Wallace AC, Laskowski RA, Thornton JM. LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng. 1995 Feb;8(2):127–134.
   PubMedGoogle Scholar
• Kollman PA, Massova I, Reyes C, et al. Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models. Acc Chem Res. 2000 Dec;33(12):889–897.
   PubMed Web of Science ®Google Scholar
• Kumari R, Kumar R. Open source drug discovery C, et al. g_mmpbsa–a GROMACS tool for high-throughput MM-PBSA calculations. J Chem Inform Model. 2014 Jul 28;54(7):1951–1962.
   PubMed Web of Science ®Google Scholar
• Wang B, Li L, Hurley TD, et al. Molecular recognition in a diverse set of protein-ligand interactions studied with molecular dynamics simulations and end-point free energy calculations. J Chem Inform Model. 2013 Oct 28;53(10):2659–2670.
   PubMed Web of Science ®Google Scholar
• Szondy Z, Korponay-Szabo I, Kiraly R, et al. Transglutaminase 2 in human diseases. Biomed (Taipei). 2017 Sep;7(3):15.
   PubMedGoogle Scholar
• Kanchan K, Fuxreiter M, Fesus L. Physiological, pathological, and structural implications of non-enzymatic protein-protein interactions of the multifunctional human transglutaminase 2. Cell Mol Life Sci. 2015 Aug;72(16):3009–3035.
   PubMed Web of Science ®Google Scholar
• Wang Z, Griffin M. TG2, a novel extracellular protein with multiple functions. Amino Acids. 2012 Feb;42(2–3):939–949.
   PubMed Web of Science ®Google Scholar
• Budillon A, Carbone C, Di Gennaro E. Tissue transglutaminase: a new target to reverse cancer drug resistance. Amino Acids. 2013 Jan;44(1):63–72.
   PubMed Web of Science ®Google Scholar
• Johnson TS, Fisher M, Haylor JL, et al. Transglutaminase inhibition reduces fibrosis and preserves function in experimental chronic kidney disease. J Am Soc Nephrol. 2007 Dec;18(12):3078–3088.
   PubMed Web of Science ®Google Scholar
• Fell S, Wang Z, Blanchard A, et al. Transglutaminase 2: a novel therapeutic target for idiopathic pulmonary fibrosis using selective small molecule inhibitors. Amino Acids. 2021 Feb;53(2):205–217.
   PubMed Web of Science ®Google Scholar
• Wang Z, Stuckey DJ, Murdoch CE, et al. Cardiac fibrosis can be attenuated by blocking the activity of transglutaminase 2 using a selective small-molecule inhibitor. Cell Death Dis. 2018 Apr 27;9(6):613.
   PubMed Web of Science ®Google Scholar
• Duval E, Case A, Stein RL, et al. Structure-activity relationship study of novel tissue transglutaminase inhibitors. Bioorg Med Chem Lett. 2005 Apr 1;15(7):1885–1889.
   PubMed Web of Science ®Google Scholar
• Jeitner TM, Delikatny EJ, Ahlqvist J, et al. Mechanism for the inhibition of transglutaminase 2 by cystamine. Biochem Pharmacol. 2005 Mar 15;69(6):961–970.
   PubMed Web of Science ®Google Scholar
• Bailey CD, Johnson GV. The protective effects of cystamine in the R6/2 Huntington's disease mouse involve mechanisms other than the inhibition of tissue transglutaminase. Neurobiol Aging. 2006 Jun;27(6):871–879.
   PubMed Web of Science ®Google Scholar
• Castelhano AL, Billedeau R, Pliura DH, et al. Synthesis, chemistry, and absolute configuration of novel transglutaminase inhibitors containing a 3-halo-4,5-dihydroisoxazole. Bioorg Chem. 1988 Sep;16(3):335–340.
   Web of Science ®Google Scholar
• Choi K, Siegel M, Piper JL, et al. Chemistry and biology of dihydroisoxazole derivatives: selective inhibitors of human transglutaminase 2. Chem Biol. 2005 Apr;12(4):469–475.
   PubMed Web of Science ®Google Scholar
• Kim N, Kang JH, Lee WK, et al. Allosteric inhibition site of transglutaminase 2 is unveiled in the N terminus. Amino Acids. 2018 Nov;50(11):1583–1594.
   PubMed Web of Science ®Google Scholar
• Case A, Stein RL. Kinetic analysis of the interaction of tissue transglutaminase with a nonpeptidic slow-binding inhibitor. Biochemistry. 2007 Jan 30;46(4):1106–1115.
   PubMed Web of Science ®Google Scholar
• Lai TS, Slaughter TF, Peoples KA, et al. Regulation of human tissue transglutaminase function by magnesium-nucleotide complexes. identification of distinct binding sites for Mg-GTP and Mg-ATP. J Biol Chem. 1998 Jan 16;273(3):1776–1781.
   PubMed Web of Science ®Google Scholar
• Lortat-Jacob H, Burhan I, Scarpellini A, et al. Transglutaminase-2 interaction with heparin: identification of a heparin binding site that regulates cell adhesion to fibronectin-transglutaminase-2 matrix. J Biol Chem. 2012 May 25;287(22):18005–18017.
   PubMed Web of Science ®Google Scholar
• Wang Z, Collighan RJ, Pytel K, et al. Characterization of heparin-binding site of tissue transglutaminase: its importance in cell surface targeting, matrix deposition, and cell signaling. J Biol Chem. 2012 Apr 13;287(16):13063–13083.
   PubMed Web of Science ®Google Scholar
• Takai Y, Sasaki T, Matozaki T. Small GTP-binding proteins. Physiol Rev. 2001 Jan;81(1):153–208.
   PubMed Web of Science ®Google Scholar