Inhibition of methionyl-tRNA synthetase by REP8839 and effects of resistance mutations on enzyme activity

Antimicrobial Agents and Chemotherapy

Volumn 53, Issue 1, 2009, Pages 86-94

  Green, Louis S ^a   Bullard, James M ^a   Ribble, Wendy ^a   Dean, Frank ^a   Ayers, David F ^a   Ochsner, Urs A ^a   Janjic, Nebojsa ^a   Jarvis, Thale C ^a  

^a Replidyne Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; ANTIINFECTIVE AGENT; METHIONINE; METHIONINE TRANSFER RNA LIGASE; REP 8839; UNCLASSIFIED DRUG;

AMINOACYLATION; ARTICLE; BACILLUS ANTHRACIS; BACTERIAL STRAIN; CONTROLLED STUDY; DRUG BINDING; DRUG STRUCTURE; ENZYME ACTIVITY; ENZYME INHIBITION; MUTATIONAL ANALYSIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; STAPHYLOCOCCUS AUREUS; STREPTOCOCCUS PNEUMONIAE;

ADENOSINE TRIPHOSPHATE; ANTI-BACTERIAL AGENTS; DIAMINES; HUMANS; METHIONINE; METHIONINE-TRNA LIGASE; MOLECULAR STRUCTURE; MUTATION; STAPHYLOCOCCUS AUREUS; STRUCTURE-ACTIVITY RELATIONSHIP; THIOPHENES;

EID: 59749087749     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00275-08     Document Type: Article

References (46)

1. Blanquet, S., G. Fayat, and J. P. Waller. 1974. The mechanism of action of methionyl-tRNA synthetase from Escherichia coli. Mechanism of the amino-acid activation reaction catalyzed by the native and the trypsin-modified enzymes. Eur. J. Biochem. 44:343-351.
2. Blanquet, S., G. Fayat, and J. P. Waller. 1975. The amino acid activation reaction catalyzed by methionyl-transfer RNA synthetase: evidence for synergistic coupling between the sites for methionine adenosine and pyrophosphate. J. Mol. Biol. 94:1-15.
3. Blanquet, S., M. Iwatsubo, and J. P. Waller. 1973. The mechanism of action of methionyl-tRNA synthetase from Escherichia coli. 1. Fluorescence studies on tRNAMet binding as a function of ligands, ions and pH. Eur. J. Biochem. 36:213-226.
4. Brown, J. R., D. Gentry, J. A. Becker, K. Ingraham, D. J. Holmes, and M. J. Stanhope. 2003. Horizontal transfer of drug-resistant aminoacyl-transfer-RNA synthetases of anthrax and Gram-positive pathogens. EMBO Rep. 4:692-698.
5. Bullard, J. M., Y. C. Cai, B. Demeler, and L. L. Spremulli. 1999. Expression and characterization of a human mitochondrial phenylalanyl-tRNA synthetase. J. Mol. Biol. 288:567-577.
6. I) and the concentration of inhibitor which causes 50 per cent inhibition (IC50) of an enzymatic reaction. Biochem. Pharmacol. 22:3099-3108.
7. Crepin, T., E. Schmitt, S. Blanquet, and Y. Mechulam. 2002. Structure and function of the C-terminal domain of methionyl-tRNA synthetase. Biochemistry 41:13003-13011.
8. Crepin, T., E. Schmitt, S. Blanquet, and Y. Mechulam. 2004. Three-dimensional structure of methionyl-tRNA synthetase from Pyrococcus abyssi. Biochemistry 43:2635-2644.
9. Crepin, T., E. Schmitt, Y. Mechulam, P. B. Sampson, M. D. Vaughan, J. F. Honek, and S. Blanquet. 2003. Use of analogues of methionine and methionyl adenylate to sample conformational changes during catalysis in Escherichia coli methionyl-tRNA synthetase. J. Mol. Biol. 332:59-72.
10. Critchley, I. A., C. L. Young, K. C. Stone, U. A. Ochsner, J. Guiles, T. Tarasow, and N. Janjic. 2005. Antibacterial activity of REP8839, a new antibiotic for topical use. Antimicrob. Agents Chemother. 49:4247-4252.
11. Cull, M., and C. S. McHenry. 1990. Preparation of extracts from prokaryotes. Methods Enzymol. 182:147-153.
12. Cusack, S., M. Hartlein, and R. Leberman. 1991. Sequence, structural and evolutionary relationships between class 2 aminoacyl-tRNA synthetases. Nucleic Acids Res. 19:3489-3498.
13. Eriani, G., M. Delarue, O. Poch, J. Gangloff, and D. Moras. 1990. Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs. Nature 347:203-206.
14. Finn, J., K. Mattia, M. Morytko, S. Ram, Y. Yang, X. Wu, E. Mak, P. Gallant, and D. Keith. 2003. Discovery of a potent and selective series of pyrazole bacterial methionyl-tRNA synthetase inhibitors. Bioorg. Med. Chem. Lett. 13:2231-2234.
15. Gentry, D. R., K. A. Ingraham, M. J. Stanhope, S. Rittenhouse, R. L. Jarvest, P. J. O'Hanlon, J. R. Brown, and D. J. Holmes. 2003. Variable sensitivity to bacterial methionyl-tRNA synthetase inhibitors reveals subpopulations of Streptococcus pneumoniae with two distinct methionyl-tRNA synthetase genes. Antimicrob. Agents Chemother. 47:1784-1789.
16. Iwatsuki, K., O. Yamasaki, S. Morizane, and T. Oono. 2006. Staphylococcal cutaneous infections: invasion, evasion and aggression. J. Dermatol. Sci. 42:203-214.
17. Jakubowski, H. 2000. Translational incorporation of S-nitrosohomocysteine into protein. J. Biol. Chem. 275:21813-21816.
18. Jarvest, R. L., J. M. Berge, V. Berry, H. F. Boyd, M. J. Brown, J. S. Elder, A. K. Forrest, A. P. Fosberry, D. R. Gentry, M. J. Hibbs, D. D. Jaworski, P. J. O'Hanlon, A. J. Pope, S. Rittenhouse, R. J. Sheppard, C. Slater-Radosti, and A. Worby. 2002. Nanomolar inhibitors of Staphylococcus aureus methionyl tRNA synthetase with potent antibacterial activity against gram-positive pathogens. J. Med. Chem. 45:1959-1962.
19. Jarvest, R. L., J. M. Berge, M. J. Brown, P. Brown, J. S. Elder, A. K. Forrest, C. S. Houge-Frydrych, P. J. O'Hanlon, D. J. McNair, S. Rittenhouse, and R. J. Sheppard. 2003. Optimisation of aryl substitution leading to potent methionyl tRNA synthetase inhibitors with excellent gram-positive antibacterial activity. Bioorg. Med. Chem. Lett. 13:665-668.
20. Jarvis, T. C., L. S. Green, J. M. Bullard, W. Ribble, and N. Janjic. 2006. Selectivity and potency of methionyl tRNA synthetase inhibition by REP8839. Abstr. 46th Intersci. Conf. Antimicrob. Agents Chemother., abstr. F1-1969.
21. Kalogerakos, T., P. Dessen, G. Fayat, and S. Blanquet. 1980. Proteolytic cleavage of methionyl transfer ribonucleic acid synthetase from Bacillus stearothermophilus: effects on activity and structure. Biochemistry 19:3712-3723.
22. Kohda, D., S. Yokoyama, and T. Miyazawa. 1987. Functions of isolated domains of methionyl-tRNA synthetase from an extreme thermophile, Thermus thermophilus HB8. J. Biol. Chem. 262:558-563.
23. Le, J., and J. M. Lieberman. 2006. Management of community-associated methicillin-resistant Staphylococcus aureus infections in children. Pharmacotherapy 26:1758-1770.
24. Lee, J., M. K. Kang, M. W. Chun, Y. J. Jo, J. H. Kwak, and S. Kim. 1998. Methionine analogues as inhibitors of methionyl-tRNA synthetase. Bioorg. Med. Chem. Lett. 8:3511-3514.
25. Lee, J., S. U. Kang, M. K. Kang, M. W. Chun, Y. J. Jo, J. H. Kwak, and S. Kim. 1999. Methionyl adenylate analogues as inhibitors of methionyl-tRNA synthetase. Bioorg. Med. Chem. Lett. 9:1365-1370.
26. Mechulam, Y., E. Schmitt, L. Maveyraud, C. Zelwer, O. Nureki, S. Yokoyama, M. Konno, and S. Blanquet. 1999. Crystal structure of Escherichia coli methionyl-tRNA synthetase highlights species-specific features. J. Mol. Biol. 294:1287-1297.
27. Mechulam, Y., E. Schmitt, M. Panvert, J. M. Schmitter, M. Lapadat-Tapolsky, T. Meinnel, P. Dessen, S. Blanquet, and G. Fayat. 1991. MethionyltRNA synthetase from Bacillus stearothermophilus: structural and functional identities with the Escherichia coli enzyme. Nucleic Acids Res. 19:3673-3681.
28. Meinnel, T., Y. Mechulam, F. Dardel, J. M. Schmitter, C. Hountondji, S. Brunie, P. Dessen, G. Fayat, and S. Blanquet. 1990. Methionyl-tRNA synthetase from E. coli - a review. Biochimie 72:625-632.
29. Mulvey, R. S., and A. R. Fersht. 1976. Subunit interactions in the methionyl-tRNA synthetase of Bacillus stearothermophilus. Biochemistry 15:243-249.
30. Mulvey, R. S., and A. R. Fersht. 1978. Mechanism of aminoacylation of transfer RNA. A pre-steady-state analysis of the reaction pathway catalyzed by the methionyl-tRNA synthetase of Bacillus stearothermophilus. Biochemistry 17:5591-5597.
31. Myers, E. W., and W. Miller. 1988. Optimal alignments in linear space. Comput. Appl. Biosci. 4:11-17.
32. Nureki, O., T. Kohno, K. Sakamoto, T. Miyazawa, and S. Yokoyama. 1993. Chemical modification and mutagenesis studies on zinc binding of aminoacyl-tRNA synthetases. J. Biol. Chem. 268:15368-15373.
33. Ochsner, U. A., X. Sun, T. Jarvis, I. Critchley, and N. Janjic. 2007. Aminoacyl-tRNA synthetases: essential and still promising targets for new antiinfective agents. Expert Opin. Investig. Drugs 16:573-593.
34. Ochsner, U. A., C. L. Young, K. C. Stone, F. B. Dean, N. Janjic, and I. A. Critchley. 2005. Mode of action and biochemical characterization of REP8839, a novel inhibitor of methionyl-tRNA synthetase. Antimicrob. Agents Chemother. 49:4253-4262.
35. Pohlmann, J., and H. Brotz-Oesterhelt. 2004. New aminoacyl-tRNA synthetase inhibitors as antibacterial agents. Curr. Drug Targets Infect. Disord. 4:261-272.
36. Pope, A. J., K. J. Moore, M. McVey, L. Mensah, N. Benson, N. Osbourne, N. Broom, M. J. Brown, and P. O'Hanlon. 1998. Characterization of isoleucyl-tRNA synthetase from Staphylococcus aureus. II. Mechanism of inhibition by reaction intermediate and pseudomonic acid analogues studied using transient and steady-state kinetics. J. Biol. Chem. 273:31691-31701.
37. Rice, L. B. 2006. Antimicrobial resistance in gram-positive bacteria. Am. J. Infect. Control 34:S11-S19.
38. Rogers, R. L., and J. Perkins. 2006. Skin and soft tissue infections. Prim. Care 33:697-710.
39. Rosen, T. 2005. Update on treating uncomplicated skin and skin structure infections. J. Drugs Dermatol. 4:s9-s14.
40. Sabol, K. E., K. L. Echevarria, and J. S. Lewis. 2006. Community-associated methicillin-resistant Staphylococcus aureus: new bug, old drugs. Ann. Pharmacother. 40:1125-1133.
41. Schmitt, E., M. Panvert, Y. Mechulam, and S. Blanquet. 1997. General structure/function properties of microbial methionyl-tRNA synthetases. Eur. J. Biochem. 246:539-547.
42. Spencer, A. C., A. Heck, N. Takeuchi, K. Watanabe, and L. L. Spremulli. 2004. Characterization of the human mitochondrial methionyl-tRNA synthetase. Biochemistry 43:9743-9754.
43. Tandon, M., D. L. Coffen, P. Gallant, D. Keith, and M. A. Ashwell. 2004. Potent and selective inhibitors of bacterial methionyl tRNA synthetase derived from an oxazolone-dipeptide scaffold. Bioorg. Med. Chem. Lett. 14:1909-1911.
44. Thompson, J. D., D. G. Higgins, and T. J. Gibson. 1994. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22:4673-4680.
45. Vaughan, M. D., P. B. Sampson, E. Daub, and J. F. Honek. 2005. Investigation of bioisosteric effects on the interaction of substrates/ inhibitors with the methionyl-tRNA synthetase from Escherichia coli. Med. Chem. 1:227-237.
46. Vaughan, M. D., P. B. Sampson, and J. F. Honek. 2002. Methionine in and out of proteins: targets for drug design. Curr. Med. Chem. 9:385-409.