Revisiting the nucleotide and aminoglycoside substrate specificity of the bifunctional aminoglycoside acetyltransferase(6′)-Ie/aminoglycoside phosphotransferase(2″)-Ia enzyme

Journal of Biological Chemistry

Volumn 287, Issue 52, 2012, Pages 43262-43269

  Frase, Hilary ^a   Toth, Marta ^a   Vakulenko, Sergei B ^a  

^a UNIVERSITY OF NOTRE DAME   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOGLYCOSIDE ACETYLTRANSFERASE; AMINOGLYCOSIDE RESISTANCE; AMINOGLYCOSIDES; BACTERIAL PATHOGENS; BACTERIAL RESISTANCE; BIFUNCTIONAL; BIFUNCTIONAL ENZYMES; BROAD SPECTRUM; CO-SUBSTRATE; GTPASE ACTIVITY; IN-VIVO; PHOSPHOTRANSFERASES; STEADY-STATE KINETICS; SUBSTRATE PROFILE; SUBSTRATE SPECIFICITY;

ANTIBIOTICS; NUCLEOTIDES; PHOSPHORYLATION; SUBSTRATES;

ENZYME ACTIVITY;

ADENOSINE TRIPHOSPHATE; AMIKACIN; AMINOGLYCOSIDE; AMINOGLYCOSIDE ACETYLTRANSFERASE (6') IE AMINOGLYCOSIDE PHOSPHOTRANSFERASE (2'') IA; BACTERIAL ENZYME; BUTIROSIN; DIBEKACIN; FRAMYCETIN; GENTAMICIN C; GUANOSINE TRIPHOSPHATE; HABEKACIN; KANAMYCIN A; KANAMYCIN B; LIVIDOMYCIN; NEAMINE; NETILMICIN; PAROMOMYCIN; SISOMICIN; TOBRAMYCIN; UNCLASSIFIED DRUG;

ANTIBIOTIC RESISTANCE; ARTICLE; CONCENTRATION RESPONSE; DRUG EFFECT; DRUG STRUCTURE; ENZYME ACTIVITY; ENZYME MECHANISM; ENZYME PHOSPHORYLATION; ENZYME SPECIFICITY; ENZYME STRUCTURE; ESCHERICHIA COLI; IN VIVO STUDY; MINIMUM INHIBITORY CONCENTRATION; NONHUMAN; PRIORITY JOURNAL; STAPHYLOCOCCUS AUREUS; STEADY STATE; SUBSTITUTION REACTION;

ACETYLTRANSFERASES; ADENOSINE TRIPHOSPHATE; AMINOGLYCOSIDES; ANTI-BACTERIAL AGENTS; BACTERIAL PROTEINS; DRUG RESISTANCE, BACTERIAL; GRAM-POSITIVE BACTERIA; GUANOSINE TRIPHOSPHATE; PHOSPHORYLATION; PHOSPHOTRANSFERASES (ALCOHOL GROUP ACCEPTOR); SUBSTRATE SPECIFICITY;

BACTERIA (MICROORGANISMS); POSIBACTERIA;

EID: 84871541597     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M112.416453     Document Type: Article

References (30)

1. Vakulenko, S. B., and Mobashery, S. (2003) Versatility of aminoglycosides and prospects for their future. Clin. Microbiol. Rev. 16, 430-450 (Pubitemid 36871315)
2. Llano-Sotelo, B., Azucena, E. F., Jr., Kotra, L. P., Mobashery, S., and Chow, C. S. (2002) Aminoglycosides modified by resistance enzymes display diminished binding to the bacterial ribosomal aminoacyl-tRNA site. Chem. Biol. 9, 455-463 (Pubitemid 34439764)
3. Culebras, E., and Martínez, J. L. (1999) Aminoglycoside resistance mediated by the bifunctional enzyme 6′-N-aminoglycoside acetyltransferase-2″-O-aminoglycoside phosphotransferase. Front Biosci. 4, D1-D8
4. Zhang, W., Fisher, J. F., and Mobashery, S. (2009) The bifunctional enzymes of antibiotic resistance. Curr. Opin. Microbiol. 12, 505-511
5. Boehr, D. D., Daigle, D. M., and Wright, G. D. (2004) Domain-domain interactions in the aminoglycoside antibiotic resistance enzyme AAC(6′)-APH(2″). Biochemistry 43, 9846-9855 (Pubitemid 38993834)
6. Daigle, D. M., Hughes, D. W., and Wright, G. D. (1999) Prodigious substrate specificity of AAC(6′)-APH(2″), an aminoglycoside antibiotic resistance determinant in enterococci and staphylococci. Chem. Biol. 6, 99-110 (Pubitemid 29363160)
7. Azucena, E., Grapsas, I., and Mobashery, S. (1997) Properties of a bifunctional bacterial antibiotic resistance enzyme that catalyzes ATP-dependent 2″-phosphorylation and acetyl-CoA-dependent 6′-acetylation of aminoglycosides. J. Am. Chem. Soc. 119, 2317-2318 (Pubitemid 27160011)
8. Chow, J. W. (2000) Aminoglycoside resistance in enterococci. Clin. Infect. Dis. 31, 586-589
9. Martel, A., Masson, M., Moreau, N., and Le Goffic, F. (1983) Kinetic studies of aminoglycoside acetyltransferase and phosphotransferase from Staphylococcus aureus RPAL. Relationship between the two activities. Eur. J. Biochem. 133, 515-521 (Pubitemid 13060120)
10. Toth, M., Chow, J. W., Mobashery, S., and Vakulenko, S. B. (2009) Source of phosphate in the enzymic reaction as a point of distinction among aminoglycoside 2″-phosphotransferases. J. Biol. Chem. 284, 6690-6696
11. Badarau, A., Shi, Q., Chow, J. W., Zajicek, J., Mobashery, S., and Vakulenko, S. (2008) Aminoglycoside 2″-phosphotransferase type IIIa from Enterococcus. J. Biol. Chem. 283, 7638-7647
12. Toth, M., Zajicek, J., Kim, C., Chow, J. W., Smith, C., Mobashery, S., and Vakulenko, S. (2007) Kinetic mechanism of enterococcal aminoglycoside phosphotransferase 2″-Ib. Biochemistry 46, 5570-5578 (Pubitemid 46717279)
13. Toth, M., Frase, H., Antunes, N. T., Smith, C. A., and Vakulenko, S. B. (2010) Crystal structure and kinetic mechanism of aminoglycoside phosphotransferase-2″-IVa. Protein Sci. 19, 1565-1576
14. Clinical and Laboratory Standards Institute (2009). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically: Approved Standard, 8th Ed., Clinical and Laboratory Standards Institute, Wayne, PA
15. Dixon, M. (1953) The determination of enzyme inhibitor constants. Biochem. J. 55, 170-171
16. Copeland, R. A. (2000) Enzymes: A Practical Introduction to Structure, Mechanism, and Data Analysis, 2nd Ed., pp. 310-313, John Wiley&Sons, Inc., New York
17. Gilbert, S. P., and Mackey, A. T. (2000) Kinetics: a tool to study molecular motors. Methods 22, 337-354 (Pubitemid 32896699)
18. Ubukata, K., Yamashita, N., Gotoh, A., and Konno, M. (1984) Purification and characterization of aminoglycoside-modifying enzymes from Staphylococcus aureus and Staphylococcus epidermidis. Antimicrob. Agents Chemother. 25, 754-759 (Pubitemid 14112042)
19. Rouch, D. A., Byrne, M. E., Kong, Y. C., and Skurray, R. A. (1987) The aacA-aphD gentamicin and kanamycin resistance determinant of Tn4001 from Staphylococcus aureus: expression and nucleotide sequence analysis. J. Gen. Microbiol. 133, 3039-3052 (Pubitemid 18049450)
20. Bochner, B. R., and Ames, B. N. (1982) Complete analysis of cellular nucleotides by two-dimensional thin layer chromatography. J. Biol. Chem. 257, 9759-9769 (Pubitemid 13205141)
21. Buckstein, M. H., He, J., and Rubin, H. (2008) Characterization of nucleotide pools as a function of physiological state in Escherichia coli. J. Bacteriol. 190, 718-726 (Pubitemid 351360088)
22. Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., and Rabinowitz, J. D. (2009) Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli. Nat. Chem. Biol. 5, 593-599
23. De Mey, M., Taymaz-Nikerel, H., Baart, G., Waegeman, H., Maertens, J., Heijnen, J. J., and van Gulik, W. M. (2010) Catching prompt metabolite dynamics in Escherichia coli with the BioScope at oxygen rich conditions. Metab. Eng. 12, 477-487
24. Liebeke, M., Meyer, H., Donat, S., Ohlsen, K., and Lalk, M. (2010) A metabolomic view of Staphylococcus aureus and its Ser/Thr kinase and phosphatase deletion mutants: involvement in cell wall biosynthesis. Chem. Biol. 17, 820-830
25. Young, P. G., Walanj, R., Lakshmi, V., Byrnes, L. J., Metcalf, P., Baker, E. N., Vakulenko, S. B., and Smith, C. A. (2009) The crystal structures of substrate and nucleotide complexes of Enterococcus faecium aminoglycoside- 2″-phosphotransferase-IIa [APH(2″)-IIa] provide insights into substrate selectivity in the APH(2″) subfamily. J. Bacteriol. 191, 4133-4143
26. Smith, C. A., Toth, M., Frase, H., Byrnes, L. J., and Vakulenko, S. B. (2012) Aminoglycoside 2″-phosphotransferase IIIa (APH(2″) -IIIa) prefers GTP over ATP: structural templates for nucleotide recognition in the bacterial aminoglycoside-2″ kinases. J. Biol. Chem. 287, 12893-12903
27. Hotta, K., Zhu, C. B., Ogata, T., Sunada, A., Ishikawa, J., Mizuno, S., Ikeda, Y., and Kondo, S. (1996) Enzymatic 2′-N-acetylation of arbekacin and antibiotic activity of its product. J. Antibiot. 49, 458-464
28. Hotta, K., Sunada, A., Ikeda, Y., and Kondo, S. (2000) Double stage activity in aminoglycoside antibiotics. J. Antibiot. 53, 1168-1174
29. Kim, C., Cha, J. Y., Yan, H., Vakulenko, S. B., and Mobashery, S. (2006) Hydrolysis of ATP by aminoglycoside 3′-phosphotransferases: an unexpected cost to bacteria for harboring an antibiotic resistance enzyme. J. Biol. Chem. 281, 6964-6969 (Pubitemid 43847458)
30. Matsuo, H., Kobayashi, M., Kumagai, T., Kuwabara, M., and Sugiyama, M. (2003) Molecular mechanism for the enhancement of arbekacin resistance in a methicillin-resistant Staphylococcus aureus. FEBS Lett. 546, 401-406 (Pubitemid 36782447)