The genomic enzymology of antibiotic resistance

Annual Review of Genetics

Volumn 44, Issue , 2010, Pages 25-51

  Morar, Mariya ^a   Wright, Gerard D ^a  

^a MCMASTER UNIVERSITY   (Canada)

Author keywords

antibiotic resistance mechanism; Antibiotic resistome; enzyme structure function; proto resistance gene

Indexed keywords

AMPICILLIN; AZITHROMYCIN; AZTREONAM; CEPHALOSPORIN; CEPHAMYCIN; CHLORAMPHENICOL; CLINDAMYCIN; COLISTIN; DALFOPRISTIN PLUS QUINUPRISTIN; DAPTOMYCIN; ERYTHROMYCIN; GENTAMICIN; LINEZOLID; MEROPENEM; MINOCYCLINE; MONOBACTAM; NUCLEOSIDE MONOPHOSPHATE KINASE; PENEM DERIVATIVE; PENICILLIN G; RIFAMPICIN; RIFAMYCIN DERIVATIVE; SPECTINOMYCIN; STREPTOMYCIN; SULFAMETHOXAZOLE; TEICOPLANIN; TIGECYCLINE; TRIMETHOPRIM; VANCOMYCIN;

ADENOSINE DIPHOSPHATE RIBOSYLATION; ANTIBIOTIC RESISTANCE; DRUG STRUCTURE; ENZYMOLOGY; HOUSEKEEPING GENE; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVIEW; STRUCTURE ANALYSIS;

ANTI-BACTERIAL AGENTS; BACTERIA; BACTERIAL PROTEINS; DRUG RESISTANCE, BACTERIAL;

EID: 78149445856     PISSN: 00664197     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev-genet-102209-163517     Document Type: Review

References (155)

1. Abraham EP, Chain E. 1940. An enzyme from bacteria able to destroy penicillin. Nature 146:837
2. Allignet J, Loncle V, Mazodier P, el Solh N. 1988. Nucleotide sequence of a staphylococcal plasmid gene, vgb, encoding a hydrolase inactivating the B components of virginiamycin-like antibiotics. Plasmid 20:271-75
3. Ambler RP. 1980. The structure of beta-lactamases. Philos. Trans. R. Soc. Lond. Ser. B 289:321-31
4. Aravind L, Koonin EV. 1999. DNA polymerase beta-like nucleotidyltransferase superfamily: identification of three new families, classification and evolutionary history. Nucleic Acids Res. 27:1609-18
5. Arca P, Rico M, Brana AF, Villar CJ, Hardisson C, Suarez JE. 1988. Formation of an adduct between fosfomycin and glutathione: a new mechanism of antibiotic resistance in bacteria. Antimicrob. Agents Chemother. 32:1552-56
6. Baltz RH. 2005. Antibiotic discovery from actinomycetes: Will a renaisssance follow the decline and fall? SIMNews 55:186-96
7. Bancroft EA. 2007. Antimicrobial resistance: It's not just for hospitals. JAMA 298:1803-4
8. Bateman KP, Yang K, Thibault P, White RL, Vining LC. 1996. Inactivation of Etamycin by a novel elimination mechanism in Streptomyces lividans. J. Am. Chem. Soc. 118:5335-38
9. Baysarowich J, Koteva K, Hughes DW, Ejim L, Griffiths E, et al. 2008. Rifamycin antibiotic resistance by ADP-ribosylation: Structure and diversity of Arr. Proc. Natl. Acad. Sci. USA 105:4886-91
10. Beaman TW, Sugantino M, Roderick SL. 1998. Structure of the hexapeptide xenobiotic acetyltransferase from Pseudomonas aeruginosa. Biochemistry 37:6689-96
11. Beard WA, Wilson SH. 2006. Structure and mechanism of DNA polymerase Beta. Chem. Rev. 106:361-82
12. Benveniste R, Davies J. 1973. Aminoglycoside antibiotic-inactivating enzymes in actinomycetes similar to those present in clinical isolates of antibiotic-resistant bacteria. Proc. Natl. Acad. Sci. USA 70:2276-80
13. Bernat BA, Laughlin LT, Armstrong RN. 1999. Elucidation of a monovalent cation dependence and characterization of the divalent cation binding site of the fosfomycin resistance protein (FosA). Biochemistry 38:7462-69
14. Boehr DD, Draker KA, Koteva K, Bains M, Hancock RE, Wright GD. 2003. Broad-spectrum peptide inhibitors of aminoglycoside antibiotic resistance enzymes. Chem. Biol. 10:189-96
15. Bolam DN, Roberts S, Proctor MR, Turkenburg JP, Dodson EJ, et al. 2007. The crystal structure of two macrolide glycosyltransferases provides a blueprint for host cell antibiotic immunity. Proc. Natl. Acad. Sci. USA 104:5336-41
16. Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D, et al. 2009. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin. Infect. Dis. 48:1-12
17. Bozdogan B, Leclercq R. 1999. Effects of genes encoding resistance to streptogramins A and B on the activity of quinupristin-dalfopristin against Enterococcus faecium. Antimicrob. Agents Chemother. 43:2720-25
18. Brenner S. 1987. Phosphotransferase sequence homology. Nature 329:21
19. Brown DW, SchaabMR, Birmingham WR, Armstrong RN. 2009. Evolution of the antibiotic resistance protein, FosA, is linked to a catalytically promiscuous progenitor. Biochemistry 48:1847-49
20. Burk DL, Ghuman N, Wybenga-Groot LE, Berghuis AM. 2003. X-ray structure of the AAC(6')-Ii antibiotic resistance enzyme at 1.8 A resolution; examination of oligomeric arrangements in GNAT superfamily members. Protein Sci. 12:426-37
21. Bush K, Jacoby GA. 2010. Updated functional classification of beta-lactamases. Antimicrob. Agents Chemother. 54:969-76
22. Cameron AD, Olin B, Ridderstrom M, Mannervik B, Jones TA. 1997. Crystal structure of human glyoxalase I-evidence for gene duplication and 3D domain swapping. EMBOJ. 16:3386-95
23. Canton R. 2009. Antibiotic resistance genes from the environment: a perspective through newly identified antibiotic resistance mechanisms in the clinical setting. Clin. Microbiol. Infect. 15(Suppl. 1):20-25
24. Cao M, Bernat BA, Wang Z, Armstrong RN, Helmann JD. 2001. FosB, a cysteine-dependent fosfomycin resistance protein under the control of sigma(W), an extracytoplasmic-function sigma factor in Bacillus subtilis.J. Bacteriol. 183:2380-83
25. Carter AP, Clemons WM, Brodersen DE, Morgan-Warren RJ, Wimberly BT, Ramakrishnan V. 2000. Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics. Nature 407:340-48
26. Chen-Goodspeed M, Vanhooke JL, HoldenHM, Raushel FM. 1999. Kinetic mechanism of kanamycin nucleotidyltransferase from Staphylococcus aureus. Bioorg. Chem. 27:395-408
27. Coutinho PM, Deleury E, Davies GJ, Henrissat B. 2003. An evolving hierarchical family classification for glycosyltransferases. J. Mol. Biol. 328:307-17
28. Dabbs ER, Yazawa K, Mikami Y, Miyaji M, Morisaki N, et al. 1995. Ribosylation by mycobacterial strains as a new mechanism of rifampin inactivation. Antimicrob. Agents Chemother. 39:1007-9
29. Daigle DM, Hughes DW, Wright GD. 1999. Prodigious substrate specificity of AAC(6')-APH(2"), an aminoglycoside antibiotic resistance determinant in enterococci and staphylococci. Chem. Biol. 6:99-110
30. Daigle DM, McKay GA, Thompson PR, Wright GD. 1999. Aminoglycoside antibiotic phosphotransferases are also serine protein kinases. Chem. Biol. 6:11-18
31. Daigle DM, McKay GA, Wright GD. 1997. Inhibition of aminoglycoside antibiotic resistance enzymes by protein kinase inhibitors. J. Biol. Chem. 272:24755-58
32. Davies J, Wright GD. 1997. Bacterial resistance to aminoglycoside antibiotics. Trends Microbiol. 5:234-40
33. Davies JF 2nd, Almassy RJ, Hostomska Z, Ferre RA, Hostomsky Z. 1994. 2.3 A crystal structure of the catalytic domain of DNA polymerase beta. Cell 76:1123-33
34. Davis BD. 1987. Mechanism of action of aminoglycosides. Microbiol. Rev. 51:341-50
35. D'CostaVM, McGrann KM, Hughes DW, WrightGD. 2006. Sampling the antibiotic resistome. Science 311:374-77
36. Draker KA, Northrop DB, Wright GD. 2003. Kinetic mechanism of the GCN5-related chromosomal aminoglycoside acetyltransferase AAC(6')-Ii from Enterococcus faecium: evidence of dimer subunit cooperativity. Biochemistry 42:6565-74
37. Draker KA, Wright GD. 2004. Molecular mechanism of the enterococcal aminoglycoside 6'-N-acetyltransferase': role of GNAT-conserved residues in the chemistry of antibiotic inactivation. Biochemistry 43:446-54
38. Dreusicke D, Karplus PA, Schulz GE. 1988. Refined structure of porcine cytosolic adenylate kinase at 2.1 A resolution. J. Mol. Biol. 199:359-71
39. Dutta GN, Devriese LA. 1982. Resistance to macrolide, lincosamide and streptogramin antibiotics and degradation of lincosamide antibiotics in streptococci from bovine mastitis. J. Antimicrob. Chemother. 10:403-8
40. Etienne J, Gerbaud G, Courvalin P, Fleurette J. 1989. Plasmid-mediated resistance to fosfomycin in Staphylococcus epidermidis. FEMSMicrobiol. Lett. 52:133-37
41. Fillgrove KL, Pakhomova S, Newcomer ME, Armstrong RN. 2003. Mechanistic diversity of fosfomycin resistance in pathogenic microorganisms. J. Am. Chem. Soc. 125:15730-31
42. Fillgrove KL, Pakhomova S, Schaab MR, Newcomer ME, Armstrong RN. 2007. Structure and mechanism of the genomically encoded fosfomycin resistance protein, FosX, from Listeria monocytogenes. Biochemistry 46:8110-20
43. Fischbach MA, Walsh CT. 2009. Antibiotics for emerging pathogens. Science 325:1089-93
44. Fong DH, Berghuis AM. 2002. Substrate promiscuity of an aminoglycoside antibiotic resistance enzyme via target mimicry. EMBOJ. 21:2323-31
45. Fong DH, Berghuis AM. 2009. Structural basis of APH(3')-IIIa-mediated resistance to N1-substituted aminoglycoside antibiotics. Antimicrob. Agents Chemother. 53:3049-55
46. Fong DH, Lemke CT, Hwang J, Xiong B, Berghuis AM. 2010. Structure of the antibiotic resistance factor spectinomycin phosphotransferase from Legionella pneumophila. J. Biol. Chem. 285:9545-55
47. Gates CA, Northrop DB. 1988. Alternative substrate and inhibition kinetics of aminoglycoside nucleotidyltransferase 2"-I in support of a Theorell-Chance kinetic mechanism. Biochemistry 27:3826-33
48. Gerlt JA, Babbitt PC. 2001. Divergent evolution of enzymatic function: mechanistically diverse super-families and functionally distinct suprafamilies. Annu. Rev. Biochem. 70:209-46
49. Gerratana B, Frey PA, Cleland WW. 2001. Characterization of the transition-state structure of the reaction of kanamycin nucleotidyltransferase by heavy-atom kinetic isotope effects. Biochemistry 40:2972-77
50. Hall BG, Barlow M. 2003. Structure-based phylogenies of the serine beta-lactamases. J. Mol. Evol. 57:255-60
51. Hall BG, Barlow M. 2004. Evolution of the serine beta-lactamases: past, present and future. Drug Resist. Updates 7:111-23
52. Hall BG, Salipante SJ, Barlow M. 2003. The metallo-beta-lactamases fall into two distinct phylogenetic groups. J. Mol. Evol. 57:249-54
53. Hall BG, Salipante SJ, Barlow M. 2004. Independent origins of subgroup Bl + B2 and subgroup B3 metallo-beta-lactamases. J. Mol. Evol. 59:133-41
54. Han S, Eltis LD, Timmis KN, Muchmore SW, Bolin JT. 1995. Crystal structure of the biphenyl-cleaving extradiol dioxygenase from a PCB-degrading pseudomonad. Science 270:976-80
55. Hansen JL, Moore PB, Steitz TA. 2003. Structures of five antibiotics bound at the peptidyl transferase center of the large ribosomal subunit.J. Mol. Biol. 330:1061-75
56. Hartmann MD, Bourenkov GP, Oberschall A, Strizhov N, Bartunik HD. 2006. Mechanism of phos-phoryl transfer catalyzed by shikimate kinase from Mycobacterium tuberculosis. J. Mol. Biol. 364:411-23
57. Hegde SS, Dam TK, Brewer CF, Blanchard JS. 2002. Thermodynamics of aminoglycoside and acyl-coenzyme A binding to the Salmonella enterica AAC(6')-Iy aminoglycoside N-acetyltransferase. Biochemistry 41:7519-27
58. Hegde SS, Javid-Majd F, Blanchard JS. 2001. Overexpression and mechanistic analysis of chromosomally encoded aminoglycoside 2'-N-acetyltransferase (AAC(2')-Ic) from Mycobacterium tuberculosis. J. Biol. Chem. 276:45876-81
59. Hegreness M, Shoresh N, Damian D, Hartl D, Kishony R. 2008. Accelerated evolution of resistance in multidrug environments. Proc. Natl. Acad. Sci. USA 105:13977-81
60. Holbourn KP, Shone CC, Acharya KR. 2006. A family of killer toxins. Exploring the mechanism of ADP-ribosylating toxins. FEBSJ. 273:4579-93
61. Holm L, Sander C. 1995. DNA polymerase beta belongs to an ancient nucleotidyltransferase superfamily. Trends Biochem. Sci. 20:345-47
62. Hon WC, McKay GA, Thompson PR, Sweet RM, Yang DS, et al. 1997. Structure of an enzyme required for aminoglycoside antibiotic resistance reveals homology to eukaryotic protein kinases. Cell 89:887-95
63. Izard T, Ellis J. 2000. The crystal structures of chloramphenicol phosphotransferase reveal a novel inactivation mechanism. EMBOJ. 19:2690-700
64. Jenkins G, Cundliffe E. 1991. Cloning and characterization of two genes from Streptomyces lividans that confer inducible resistance to lincomycin and macrolide antibiotics. Gene 108:55-62
65. Jogl G, Hsiao YS, Tong L. 2004. Structure and function of carnitine acyltransferases. Ann. NY Acad. Sci. 1033:17-29
66. Jogl G, Tong L. 2003. Crystal structure of carnitine acetyltransferase and implications for the catalytic mechanism and fatty acid transport. Cell 112:113-22
67. Jørgensen R, Purdy AE, Fieldhouse RJ, Kimber MS, Bartlett DH, Merrill AR. 2008. Cholix toxin, a novel ADP-ribosylating factor from Vibrio cholerae. J. Biol. Chem. 283:10671-78
68. Kajander T, Merckel MC, Thompson A, Deacon AM, Mazur P, et al. 2002. The structure of Neurospora crassa 3-carboxy-cis, cis-muconate lactonizing enzyme, a beta propeller cycloisomerase. Structure 10:483-92
69. Kannan N, Taylor SS, Zhai Y, Venter JC, Manning G. 2007. Structural and functional diversity of the microbial kinome. PLoS Biol. 5:e17
70. Kato-Murayama M, Bessho Y, Shirouzu M, Yokoyama S. 2005. Crystal structure of the RNA 2'-phosphotransferase from Aeropyrumpernix K1.J. Mol. Biol. 348:295-305
71. Kehoe LE, Snidwongse J, Courvalin P, Rafferty JB, Murray IA. 2003. Structural basis of Synercid (quinupristin-dalfopristin) resistance in Gram-positive bacterial pathogens. J. Biol. Chem. 278:29963-70
72. Kelly JA, Dideberg O, Charlier P, Wery JP, Libert M, et al. 1986. On the origin of bacterial resistance to penicillin: comparison of a beta-lactamase and a penicillin target. Science 231:1429-31
73. Kisker C, Schindelin H, Alber BE, FerryJG, Rees DC. 1996. Aleft-hand beta-helix revealed by the crystal structure of a carbonic anhydrase from the archaeon Methanosarcina thermophila. EMBOJ. 15:2323-30
74. Kleanthous C, Cullis PM, Shaw WV. 1985. 3-(Bromoacetyl)chloramphenicol, an active site directed inhibitor for chloramphenicol acetyltransferase. Biochemistry 24:5307-13
75. Kleanthous C, Shaw WV. 1984. Analysis of the mechanism of chloramphenicol acetyltransferase by steady-state kinetics. Evidence for a ternary-complex mechanism. Biochem. J. 223:211-20
76. Korczynska M, Mukhtar TA, Wright GD, Berghuis AM. 2007. Structural basis for streptogramin B resistance in Staphylococcus aureus by virginiamycin B lyase. Proc. Natl. Acad. Sci. USA 104:10388-93
77. Krell T, CogginsJR, Lapthorn AJ. 1998. The three-dimensional structure of shikimate kinase. J. Mol. Biol. 278:983-97
78. Ku SY, Yip P, Cornell KA, Riscoe MK, Behr JB, et al. 2007. Structures of 5-methylthioribose kinase reveal substrate specificity and unusual mode of nucleotide binding. J. Biol. Chem. 282:22195-206
79. Kuo MS, Chirby DG, Argoudelis AD, Cialdella JI, Coats JH, Marshall VP. 1989. Microbial glycosylation of erythromycin A Antimicrob. AgentsChemother 33 2089-91
80. Leclercq R, Carlier C, Duval J, Courvalin P. 1985. Plasmid-mediated resistance to lincomycin by inac-tivation in Staphylococcus haemolyticus. Antimicrob. Agents Chemother. 28:421-24
81. Leslie AG. 1990. Refined crystal structure of type III chloramphenicol acetyltransferase at 1.75 A resolution. J. Mol. Biol. 213:167-86
82. Leslie AG, Moody PC, Shaw WV. 1988. Structure of chloramphenicol acetyltransferase at 1.75-A resolution. Proc. Natl. Acad. Sci. USA 85:4133-37
83. Lewendon A, Murray IA, Kleanthous C, Cullis PM, Shaw WV. 1988. Substitutions in the active site of chloramphenicol acetyltransferase: role of a conserved aspartate. Biochemistry 27:7385-90
84. Li M, Dyda F, Benhar I, Pastan I, Davies DR. 1996. Crystal structure of the catalytic domain ofPseu-domonas exotoxin A complexed with a nicotinamide adenine dinucleotide analog: implications for the activation process and for ADP ribosylation. Proc. Natl. Acad. Sci. USA 93:6902-6
85. Lipka M, Filipek R, Bochtler M. 2008. Crystal structure and mechanism of the Staphylococcus cohnii virginiamycin B lyase (Vgb). Biochemistry 47:4257-65
86. Magnet S, BlanchardJS. 2005. Molecular insights into aminoglycoside action and resistance. Chem. Rev. 105:477-98
87. Magnet S, Lambert T, Courvalin P, BlanchardJS. 2001. Kinetic and mutagenic characterization of the chromosomally encoded Salmonella enterica AAC(6')-Iy aminoglycoside N-acetyltransferase. Biochemistry 40:3700-9
88. Malito E, Sekulic N, Too WC, Konrad M, Lavie A. 2006. Elucidation of human choline kinase crystal structures in complex with the products ADP or phosphocholine. J. Mol. Biol. 364:136-51
89. Martinez JL, Sanchez MB, Martínez-SolanoL, Hernandez A, GarmendiaL, etal. 2009. Functional role of bacterial multidrug efflux pumps in microbial natural ecosystems. FEMS Microbiol. Rev. 33:430-49
90. Massova I, Mobashery S. 1998. Kinship and diversification of bacterial penicillin-binding proteins and beta-lactamases. Antimicrob. Agents Chemother. 42:1-17
91. Mattevi A, Obmolova G, Kalk KH, Teplyakov A, Hol WG 1993. Crystallographic analysis of substrate binding and catalysis in dihydrolipoyl transacetylase (E2p). Biochemistry 32:3887-901
92. Maurice F, Broutin I, Podglajen I, Benas P, Collatz E, Dardel F. 2008. Enzyme structural plasticity and the emergence of broad-spectrum antibiotic resistance. EMBO Rep. 9:344-49
93. McCarthy AA, Baker HM, Shewry SC, Patchett ML, Baker EN. 2001. Crystal structure of methylmalonyl-coenzyme A epimerase from P. shermanii: a novel enzymatic function on an ancient metal binding scaffold. Structure 9:637-46
94. McKay GA, Wright GD. 1995. Kinetic mechanism of aminoglycoside phosphotransferase type IIIa. Evidence for a Theorell-Chance mechanism. J. Biol. Chem. 270:24686-92
95. McKay GA, Wright GD. 1996. Catalytic mechanism of enterococcal kanamycin kinase (APH(3')-IIIa): viscosity, thio, and solvent isotope effects support a Theorell-Chance mechanism. Biochemistry 35:8680-85
96. Morar M, Bhullar K, Hughes DW, Junop M, Wright GD. 2009. Structure and mechanism of the lincosamide antibiotic adenylyltransferase LinB. Structure 17:1649-59
97. Mukhtar TA, Koteva KP, Hughes DW, Wright GD. 2001. Vgb from Staphylococcus aureus inactivates streptogramin B antibiotics by an elimination mechanism not hydrolysis. Biochemistry 40:8877-86
98. Mukhtar TA, Wright GD. 2005. Streptogramins, oxazolidinones, and other inhibitors of bacterial protein synthesis. Chem. Rev. 105:529-42
99. Mulichak AM, Losey HC, Walsh CT, Garavito RM. 2001. Structure of the UDP-glucosyltransferase GtfB that modifies the heptapeptide aglycone in the biosynthesis of vancomycin group antibiotics. Structure 9:547-57
100. Murray IA, Cann PA, Day PJ, Derrick JP, Sutcliffe MJ, et al. 1995. Steroid recognition by chloramphenicol acetyltransferase: engineering and structural analysis of a high affinity fusidic acid binding site. J. Mol. Biol. 254:993-1005
101. Murray IA, Hawkins AR, Keyte JW, Shaw WV. 1988. Nucleotide sequence analysis and overexpression of the gene encoding a type III chloramphenicol acetyltransferase. Biochem.J. 252:173-79
102. Murray IA, Shaw WV. 1997. O-Acetyltransferases for chloramphenicol and other natural products. Antimicrob. Agents Chemother. 41:1-6
103. Neuwald AF, Landsman D. 1997. GCN5-related histone N-acetyltransferases belong to a diverse su-perfamily that includes the yeast SPT10 protein. Trends Biochem. Sci. 22:154-55
104. Nurizzo D, Shewry SC, Perlin MH, Brown SA, Dholakia JN, et al. 2003. The crystal structure of aminoglycoside-3'-phosphotransferase-IIa, an enzyme responsible for antibiotic resistance. J. Mol. Biol. 327:491-506
105. Okamoto S, Suzuki Y. 1965. Chloramphenicol-, dihydrostreptomycin-, and kanamycin-inactivating enzymes from multiple drug-resistant Escherichia coli carrying episome 'R'. Nature 208:1301-3
106. Payne DJ, GwynnMN, Holmes DJ, Pompliano DL. 2007. Drugs forbad bugs: confronting the challenges of antibacterial discovery. Nat. Rev. Drug Discov. 6:29-40
107. Pedersen LC, Benning MM, Holden HM. 1995. Structural investigation of the antibiotic and ATP-binding sites in kanamycin nucleotidyltransferase. Biochemsitry 34:13305-11
108. Peisach D, Gee P, Kent C, Xu Z. 2003. The crystal structure of choline kinase reveals a eukaryotic protein kinase fold. Structure 11:703-13
109. Petinaki E, Guerin-Faublee V, Pichereau V, Villers C, Achard A, et al. 2008. Lincomycin resistance gene lnu(D) in Streptococcus uberis. Antimicrob. Agents Chemother. 52:626-30
110. Phuc Nguyen MC, Woerther PL, Bouvet M, Andremont A, Leclercq R, Canu A. 2009. Escherichia coli as reservoir for macrolide resistance genes. Emerg. Infect. Dis. 15:1648-50
111. Quiros LM, Aguirrezabalaga I, Olano C, Mendez C, Salas JA. 1998. Two glycosyltransferases and a glycosidase are involved in oleandomycin modification during its biosynthesis by Streptomyces antibioticus. Mol. Microbiol. 28:1177-85
112. Quiros LM, Carbajo RJ, Brana AF, Salas JA. 2000. Glycosylation of macrolide antibiotics. Purification and kinetic studies of a macrolide glycosyltransferase from Streptomyces antibioticus. J. Biol. Chem. 275:11713-20
113. Quiros LM, Carbajo RJ, Salas JA. 2000. Inversion of the anomeric configuration of the transferred sugar during inactivation of the macrolide antibiotic oleandomycin catalyzed by a macrolide glycosyltransferase. FEBS Lett. 476:186-89
114. Quiros LM, Salas JA. 1995. Biosynthesis of the macrolide oleandomycin by Streptomyces antibioticus. Purification and kinetic characterization of an oleandomycin glucosyltransferase.J. Biol. Chem. 270:18234-39
115. Radika K, Northrop DB. 1984. Substrate specificities and structure-activity relationships for acylation of antibiotics catalyzed by kanamycin acetyltransferase. Biochemistry 23:5118-22
116. Radika K, Northrop DB. 1984. The kinetic mechanism of kanamycin acetyltransferase derived from the use of alternative antibiotics and coenzymes. J. Biol. Chem. 259:12543-46
117. Raetz CR, Roderick SL. 1995. A left-handed parallel beta helix in the structure of UDP-N acetylglucosamine acyltransferase. Science 270:997-1000
118. Rife CL, Pharris RE, Newcomer ME, Armstrong RN. 2002. Crystal structure of a genomically encoded fosfomycin resistance protein (FosA) at 1.19 A resolution by MAD phasing off the L-III edge of Tl(+). J.Am. Chem. Soc. 124:11001-3
119. Roberts MC, Sutcliffe J, CourvalinP, Jensen LB, Rood J, SeppalaH. 1999. Nomenclature for macrolide and macrolide-lincosamide-streptogramin B resistance determinants. Antimicrob. Agents Chemother. 43:2823-30
120. Robicsek A, Strahilevitz J, Jacoby GA, MacielagM, Abbanat D, et al. 2006. Fluoroquinolone-modifying enzyme: a new adaptation of a common aminoglycoside acetyltransferase. Nat. Med. 12:83-88
121. SakonJ, Liao HH, Kanikula AM, Benning MM, Rayment I, Holden HM. 1993. Molecular structure of kanamycin nucleotidyltransferase determined to 3.0-A resolution. Biochemistry 32:11977-84
122. Sawaya MR, PelletierH, Kumar A, Wilson SH, Kraut J. 1994. Crystal structure of rat DNA polymerase beta: evidence for a common polymerase mechanism. Science 264:1930-35
123. ScheeffED, Bourne PE. 2005. Structural evolution of the protein kinase-like superfamily. PLoS Comput. Biol. 1:e49
124. Schlunzen F, Zarivach R, Harms J, Bashan A, Tocilj A, et al. 2001. Structural basis for the interaction of antibiotics with the peptidyl transferase center in eubacteria. Nature 413:814-21
125. Shakya T, Wright GD. 2007. Mechanism of aminoglycoside antibiotic resistance. In Aminoglycoside Antibiotics, ed. DP Arya, pp. 119-40. Hoboken: Wiley
126. Shakya T, Wright GD. 2010. Nucleotide selectivity of antibiotic kinases. Antimicrob. Agents Chemother. 54:1909-13
127. Shao H, He X, Achnine L, Blount JW, Dixon RA, Wang X. 2005. Crystal structures of a multifunctional triterpene/flavonoid glycosyltransferase from Medicago truncatula. Plant Cell 17:3141-54
128. Shaw KJ, Rather PN, Hare RS, Miller GH. 1993. Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes. Microbiol. Rev. 57:138-63
129. Sheehan D, Meade G, Foley VM, Dowd CA. 2001. Structure, function and evolution of glutathione transferases: implications for classification of nonmammalian members of an ancient enzyme superfamily. Biochem.J. 360:1-16
130. Siregar JJ, Miroshnikov K, Mobashery S. 1995. Purification, characterization, and investigation of the mechanism of aminoglycoside 3'-phosphotransferase type Ia. Biochemistry 34:12681-88
131. Steitz TA. 1998. A mechanism for all polymerases. Nature 391:231-32
132. Suarez JE, Mendoza MC. 1991. Plasmid-encoded fosfomycin resistance. Antimicrob. Agents Chemother. 35:791-95
133. Sugantino M, Roderick SL. 2002. Crystal structure of Vat(D): an acetyltransferase that inactivates strep-togramin group A antibiotics. Biochemistry 41:2209-16
134. Suzuki Y, Okamoto S. 1967. The enzymatic acetylation of chloramphenicol by the multiple drug-resistant Escherichia coli carrying R factor.J. Biol. Chem. 242:4722-30
135. Taniguchi K, Nakamura A, Tsurubuchi K, Ishii A, O'Hara K, Sawai T. 1999. Identification of functional amino acids in the macrolide 2'-phosphotransferase II. Antimicrob. Agents Chemother. 43:2063-65
136. Thompson PR, Boehr DD, Berghuis AM, Wright GD. 2002. Mechanism of aminoglycoside antibiotic kinase APH(3')-IIIa: role of the nucleotide positioning loop. Biochemistry 41:7001-7
137. Thompson PR, Hughes DW, Wright GD. 1996. Mechanism of aminoglycoside 3'-phosphotransferase type IIIa: His188 is not a phosphate-accepting residue. Chem. Biol. 3:747-55
138. Tu D, Blaha G, Moore PB, Steitz TA. 2005. Structures of MLSBK antibiotics bound to mutated large ribosomal subunits provide a structural explanation for resistance. Cell 121:257-70
139. Van Pelt JE, Iyengar R, Frey PA. 1986. Gentamicin nucleotidyltransferase. Stereochemical inversion at phosphorus in enzymatic 2'-deoxyadenylyl transfer to tobramycin. J. Biol. Chem. 261:15995-99
140. Vetting MW, de Carvalho LP, Yu M, Hegde SS, Magnet S, et al. 2005. Structure and functions of the GNAT superfamily of acetyltransferases. Arch. Biochem. Biophys. 433:212-26
141. Vetting MW, Hegde SS, Javid-Majd F, Blanchard JS, Roderick SL. 2002. Aminoglycoside 2'-N-acetyltransferase from Mycobacterium tuberculosis in complex with coenzyme A and aminoglycoside substrates. Nat. Struct. Biol. 9:653-58
142. Vetting MW, Magnet S,NievesE, RoderickSL, BlanchardJS. 2004. A bacterial acetyltransferase capable of regioselective N-acetylation of antibiotics and histones. Chem. Biol. 11:565-73
143. Vetting MW, Park CH, Hegde SS, Jacoby GA, Hooper DC, BlanchardJS. 2008. Mechanistic and structural analysis of aminoglycoside N-acetyltransferase AAC(6')-Ib and its bifunctional, fluoroquinolone-active AAC(6')-Ib-cr variant. Biochemistry 47:9825-35
144. Whitman WB, Coleman DC, Wiebe WJ. 1998. Prokaryotes: the unseen majority. Proc. Natl. Acad. Sci. USA 95:6578-83
145. Wolf E, Vassilev A, Makino Y, Sali A, Nakatani Y, Burley SK 1998. Crystal structure of a GCN5-related N-acetyltransferase: Serratia marcescens aminoglycoside 3-N-acetyltransferase. Cell 94:439-49
146. Wright GD. 2005. Bacterial resistance to antibiotics: enzymatic degradation and modification. Adv. Drug Deliv. Rev. 57:1451-70
147. Wright GD. 2007. The antibiotic resistome: the nexus of chemical and genetic diversity. Nat. Rev. Microbiol. 5:175-86
148. Wright GD, Ladak P. 1997. Overexpression and characterization of the chromosomal aminoglycoside 6'-N-acetyltransferase from Enterococcus faecium. Antimicrob. Agents Chemother. 41:956-60
149. Wright GD, Thompson PR. 1999. Aminoglycoside phosphotransferases: proteins, structure, and mechanism. Front. Biosci. 4:D9-21
150. Wu D, Govindasamy L, Lian W, Gu Y, Kukar T, et al. 2003. Structure of human carnitine acetyltrans-ferase. Molecular basis for fatty acyl transfer.J. Biol. Chem. 278:13159-65
151. Wybenga-Groot LE, Draker K, Wright GD, Berghuis AM. 1999. Crystal structure of an aminoglycoside 6'-N-acetyltransferase: defining the GCN5-related N-acetyltransferase superfamily fold. Structure 7:497-507
152. Yates SP, Jørgensen R, Andersen GR, Merrill AR. 2006. Stealth and mimicry by deadly bacterial toxins. Trends. Biochem. Sci. 31:123-33
153. Yim G, Wang HH, Davies J. 2007. Antibiotics as signaling molecules. Philos. Trans. R. Soc. Lond. Ser. B 362:1195-200
154. Young PG, Walanj R, Lakshmi V, Byrnes LJ, Metcalf P, et al. 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. 191:4133-43
155. ZhengJ, Knighton DR, ten EyckLF, Karlsson R, Xuong N, et al. 1993. Crystal structure of the catalytic subunit of cAMP-dependent protein kinase complexed with MgATP and peptide inhibitor. Biochemistry 32:2154-61