1m4d Citations

Aminoglycoside 2'-N-acetyltransferase from Mycobacterium tuberculosis in complex with coenzyme A and aminoglycoside substrates.

Nat Struct Biol 9 653-8 (2002)
Related entries: 1m44, 1m4g, 1m4i

Cited: 83 times
EuropePMC logo PMID: 12161746

Abstract

AAC(2')-Ic catalyzes the coenzyme A (CoA)-dependent acetylation of the 2' hydroxyl or amino group of a broad spectrum of aminoglycosides. The crystal structure of the AAC(2')-Ic from Mycobacterium tuberculosis has been determined in the apo enzyme form and in ternary complexes with CoA and either tobramycin, kanamycin A or ribostamycin, representing the first structures of an aminoglycoside acetyltransferase bound to a drug. The overall fold of AAC(2')-Ic places it in the GCN5-related N-acetyltransferase (GNAT) superfamily. Although the physiological function of AAC(2')-Ic is uncertain, a structural analysis of these high-affinity aminoglycoside complexes suggests that the enzyme may acetylate a key biosynthetic intermediate of mycothiol, the major reducing agent in mycobacteria, and participate in the regulation of cellular redox potential.

Reviews - 1m4d mentioned but not cited (4)

  1. Aminoglycoside modifying enzymes. Ramirez MS, Tolmasky ME. Drug Resist Updat 13 151-171 (2010)
  2. Structure and Functional Diversity of GCN5-Related N-Acetyltransferases (GNAT). Salah Ud-Din AI, Tikhomirova A, Roujeinikova A. Int J Mol Sci 17 E1018 (2016)
  3. Strategies to overcome the action of aminoglycoside-modifying enzymes for treating resistant bacterial infections. Labby KJ, Garneau-Tsodikova S. Future Med Chem 5 1285-1309 (2013)
  4. Overcoming Aminoglycoside Enzymatic Resistance: Design of Novel Antibiotics and Inhibitors. Zárate SG, De la Cruz Claure ML, Benito-Arenas R, Revuelta J, Santana AG, Bastida A. Molecules 23 E284 (2018)

Articles - 1m4d mentioned but not cited (3)

  1. SuperLigands - a database of ligand structures derived from the Protein Data Bank. Michalsky E, Dunkel M, Goede A, Preissner R. BMC Bioinformatics 6 122 (2005)
  2. Resistome analysis of Mycobacterium tuberculosis: Identification of aminoglycoside 2'-Nacetyltransferase (AAC) as co-target for drug desigining. Joshi RS, Jamdhade MD, Sonawane MS, Giri AP. Bioinformation 9 174-181 (2013)
  3. Structural and biochemical analyses of an aminoglycoside 2'-N-acetyltransferase from Mycolicibacterium smegmatis. Jeong CS, Hwang J, Do H, Cha SS, Oh TJ, Kim HJ, Park HH, Lee JH. Sci Rep 10 21503 (2020)


Reviews citing this publication (17)

  1. Structure and functions of the GNAT superfamily of acetyltransferases. Vetting MW, S de Carvalho LP, Yu M, Hegde SS, Magnet S, Roderick SL, Blanchard JS. Arch Biochem Biophys 433 212-226 (2005)
  2. The future of aminoglycosides: the end or renaissance? Houghton JL, Green KD, Chen W, Garneau-Tsodikova S. Chembiochem 11 880-902 (2010)
  3. Bacterial GCN5-Related N-Acetyltransferases: From Resistance to Regulation. Favrot L, Blanchard JS, Vergnolle O. Biochemistry 55 989-1002 (2016)
  4. Tools for glycomics: mapping interactions of carbohydrates in biological systems. Ratner DM, Adams EW, Disney MD, Seeberger PH. Chembiochem 5 1375-1383 (2004)
  5. Mycothiol: synthesis, biosynthesis and biological functions of the major low molecular weight thiol in actinomycetes. Jothivasan VK, Hamilton CJ. Nat Prod Rep 25 1091-1117 (2008)
  6. Molecular recognition of aminoglycoside antibiotics by ribosomal RNA and resistance enzymes: an analysis of x-ray crystal structures. Vicens Q, Westhof E. Biopolymers 70 42-57 (2003)
  7. Carbohydrates as the next frontier in pharmaceutical research. Werz DB, Seeberger PH. Chemistry 11 3194-3206 (2005)
  8. The genomic enzymology of antibiotic resistance. Morar M, Wright GD. Annu Rev Genet 44 25-51 (2010)
  9. New Insights in to the Intrinsic and Acquired Drug Resistance Mechanisms in Mycobacteria. Nasiri MJ, Haeili M, Ghazi M, Goudarzi H, Pormohammad A, Imani Fooladi AA, Feizabadi MM. Front Microbiol 8 681 (2017)
  10. The antibiotic resistome. Wright GD. Expert Opin Drug Discov 5 779-788 (2010)
  11. Comprehensive review of chemical strategies for the preparation of new aminoglycosides and their biological activities. Thamban Chandrika N, Garneau-Tsodikova S. Chem Soc Rev 47 1189-1249 (2018)
  12. Antimycobacterial Metabolism: Illuminating Mycobacterium tuberculosis Biology and Drug Discovery. Awasthi D, Freundlich JS. Trends Microbiol 25 756-767 (2017)
  13. LZerD Protein-Protein Docking Webserver Enhanced With de novo Structure Prediction. Christoffer C, Bharadwaj V, Luu R, Kihara D. Front Mol Biosci 8 724947 (2021)
  14. Small-Molecule Acetylation by GCN5-Related N-Acetyltransferases in Bacteria. Burckhardt RM, Escalante-Semerena JC. Microbiol Mol Biol Rev 84 e00090-19 (2020)
  15. New genetic approaches shed light on TB virulence. Murry JP, Rubin EJ. Trends Microbiol 13 366-372 (2005)
  16. Advances in adjunct therapy against tuberculosis: Deciphering the emerging role of phytochemicals. Fatima S, Kumari A, Dwivedi VP. MedComm (2020) 2 494-513 (2021)
  17. Mechanistic investigation of resistance via drug-inactivating enzymes in Mycobacterium tuberculosis. Kashyap A, Singh PK, Silakari O. Drug Metab Rev 50 448-465 (2018)

Articles citing this publication (59)

  1. Molecular mechanisms of antibiotic resistance. Wright GD. Chem Commun (Camb) 47 4055-4061 (2011)
  2. Unusual regioversatility of acetyltransferase Eis, a cause of drug resistance in XDR-TB. Chen W, Biswas T, Porter VR, Tsodikov OV, Garneau-Tsodikova S. Proc Natl Acad Sci U S A 108 9804-9808 (2011)
  3. A bacterial acetyltransferase capable of regioselective N-acetylation of antibiotics and histones. Vetting MW, Magnet S, Nieves E, Roderick SL, Blanchard JS. Chem Biol 11 565-573 (2004)
  4. X-ray structure of the AAC(6')-Ii antibiotic resistance enzyme at 1.8 A resolution; examination of oligomeric arrangements in GNAT superfamily members. Burk DL, Ghuman N, Wybenga-Groot LE, Berghuis AM. Protein Sci 12 426-437 (2003)
  5. Identification and characterization of inhibitors of the aminoglycoside resistance acetyltransferase Eis from Mycobacterium tuberculosis. Green KD, Chen W, Garneau-Tsodikova S. ChemMedChem 7 73-77 (2012)
  6. Protein surface analysis for function annotation in high-throughput structural genomics pipeline. Binkowski TA, Joachimiak A, Liang J. Protein Sci 14 2972-2981 (2005)
  7. Chemical and structural insights into the regioversatility of the aminoglycoside acetyltransferase Eis. Houghton JL, Biswas T, Chen W, Tsodikov OV, Garneau-Tsodikova S. Chembiochem 14 2127-2135 (2013)
  8. Crystal structure of mycothiol synthase (Rv0819) from Mycobacterium tuberculosis shows structural homology to the GNAT family of N-acetyltransferases. Vetting MW, Roderick SL, Yu M, Blanchard JS. Protein Sci 12 1954-1959 (2003)
  9. Effects of altering aminoglycoside structures on bacterial resistance enzyme activities. Green KD, Chen W, Garneau-Tsodikova S. Antimicrob Agents Chemother 55 3207-3213 (2011)
  10. Mechanistic and structural analysis of human spermidine/spermine N1-acetyltransferase. Hegde SS, Chandler J, Vetting MW, Yu M, Blanchard JS. Biochemistry 46 7187-7195 (2007)
  11. Evolution of insect arylalkylamine N-acetyltransferases: structural evidence from the yellow fever mosquito, Aedes aegypti. Han Q, Robinson H, Ding H, Christensen BM, Li J. Proc Natl Acad Sci U S A 109 11669-11674 (2012)
  12. Inhibition of aminoglycoside acetyltransferase resistance enzymes by metal salts. Li Y, Green KD, Johnson BR, Garneau-Tsodikova S. Antimicrob Agents Chemother 59 4148-4156 (2015)
  13. The crystal structure of Rv1347c, a putative antibiotic resistance protein from Mycobacterium tuberculosis, reveals a GCN5-related fold and suggests an alternative function in siderophore biosynthesis. Card GL, Peterson NA, Smith CA, Rupp B, Schick BM, Baker EN. J Biol Chem 280 13978-13986 (2005)
  14. The geminivirus nuclear shuttle protein NSP inhibits the activity of AtNSI, a vascular-expressed Arabidopsis acetyltransferase regulated with the sink-to-source transition. Carvalho MF, Turgeon R, Lazarowitz SG. Plant Physiol 140 1317-1330 (2006)
  15. Acceptor substrate binding revealed by crystal structure of human glucosamine-6-phosphate N-acetyltransferase 1. Wang J, Liu X, Liang YH, Li LF, Su XD. FEBS Lett 582 2973-2978 (2008)
  16. Potent Inhibitors of Acetyltransferase Eis Overcome Kanamycin Resistance in Mycobacterium tuberculosis. Willby MJ, Green KD, Gajadeera CS, Hou C, Tsodikov OV, Posey JE, Garneau-Tsodikova S. ACS Chem Biol 11 1639-1646 (2016)
  17. Structural and molecular basis for resistance to aminoglycoside antibiotics by the adenylyltransferase ANT(2″)-Ia. Cox G, Stogios PJ, Savchenko A, Wright GD. mBio 6 e02180-14 (2015)
  18. Properties and identification of antibiotic drug targets. Bakheet TM, Doig AJ. BMC Bioinformatics 11 195 (2010)
  19. Sulfonamide-Based Inhibitors of Aminoglycoside Acetyltransferase Eis Abolish Resistance to Kanamycin in Mycobacterium tuberculosis. Garzan A, Willby MJ, Green KD, Gajadeera CS, Hou C, Tsodikov OV, Posey JE, Garneau-Tsodikova S. J Med Chem 59 10619-10628 (2016)
  20. Crystal structure of TDP-fucosamine acetyltransferase (WecD) from Escherichia coli, an enzyme required for enterobacterial common antigen synthesis. Hung MN, Rangarajan E, Munger C, Nadeau G, Sulea T, Matte A. J Bacteriol 188 5606-5617 (2006)
  21. Electrostatic interactions in aminoglycoside-RNA complexes. Kulik M, Goral AM, Jasiński M, Dominiak PM, Trylska J. Biophys J 108 655-665 (2015)
  22. Rational design and synthesis of potent aminoglycoside antibiotics against resistant bacterial strains. Yan RB, Yuan M, Wu Y, You X, Ye XS. Bioorg Med Chem 19 30-40 (2011)
  23. Engineering of the yeast antioxidant enzyme Mpr1 for enhanced activity and stability. Iinoya K, Kotani T, Sasano Y, Takagi H. Biotechnol Bioeng 103 341-352 (2009)
  24. Cosubstrate tolerance of the aminoglycoside resistance enzyme Eis from Mycobacterium tuberculosis. Chen W, Green KD, Garneau-Tsodikova S. Antimicrob Agents Chemother 56 5831-5838 (2012)
  25. Structural and functional analysis of the yeast N-acetyltransferase Mpr1 involved in oxidative stress tolerance via proline metabolism. Nasuno R, Hirano Y, Itoh T, Hakoshima T, Hibi T, Takagi H. Proc Natl Acad Sci U S A 110 11821-11826 (2013)
  26. The aminoglycoside 6'-N-acetyltransferase type Ib encoded by Tn1331 is evenly distributed within the cell's cytoplasm. Dery KJ, Søballe B, Witherspoon MS, Bui D, Koch R, Sherratt DJ, Tolmasky ME. Antimicrob Agents Chemother 47 2897-2902 (2003)
  27. Mycobacterial Aminoglycoside Acetyltransferases: A Little of Drug Resistance, and a Lot of Other Roles. Sanz-García F, Anoz-Carbonell E, Pérez-Herrán E, Martín C, Lucía A, Rodrigues L, Aínsa JA. Front Microbiol 10 46 (2019)
  28. Studying aminoglycoside modification by the acetyltransferase class of resistance-causing enzymes via microarray. Barrett OJ, Pushechnikov A, Wu M, Disney MD. Carbohydr Res 343 2924-2931 (2008)
  29. Catalytic mechanism of bleomycin N-acetyltransferase proposed on the basis of its crystal structure. Oda K, Matoba Y, Noda M, Kumagai T, Sugiyama M. J Biol Chem 285 1446-1456 (2010)
  30. Influence of linker length and composition on enzymatic activity and ribosomal binding of neomycin dimers. Watkins D, Kumar S, Green KD, Arya DP, Garneau-Tsodikova S. Antimicrob Agents Chemother 59 3899-3905 (2015)
  31. Ligand promiscuity through the eyes of the aminoglycoside N3 acetyltransferase IIa. Norris AL, Serpersu EH. Protein Sci 22 916-928 (2013)
  32. Tobramycin Variants with Enhanced Ribosome-Targeting Activity. Fosso MY, Zhu H, Green KD, Garneau-Tsodikova S, Fredrick K. Chembiochem 16 1565-1570 (2015)
  33. Characterization of a mycothiol ligase mutant of Rhodococcus jostii RHA1. Dosanjh M, Newton GL, Davies J. Res Microbiol 159 643-650 (2008)
  34. 6-hydroxy to 6'''-amino tethered ring-to-ring macrocyclic aminoglycosides as probes for APH(3')-IIIa kinase. Hanessian S, Szychowski J, Campos-Reales Pineda NB, Furtos A, Keillor JW. Bioorg Med Chem Lett 17 3221-3225 (2007)
  35. Structural analysis of PseH, the Campylobacter jejuni N-acetyltransferase involved in bacterial O-linked glycosylation. Song WS, Nam MS, Namgung B, Yoon SI. Biochem Biophys Res Commun 458 843-848 (2015)
  36. Unprecedented glycosidase activity at a lectin carbohydrate-binding site exemplified by the cyanobacterial lectin MVL. Shahzad-ul-Hussan S, Cai M, Bewley CA. J Am Chem Soc 131 16500-16508 (2009)
  37. Mechanistic analysis of ghrelin-O-acyltransferase using substrate analogs. Taylor MS, Dempsey DR, Hwang Y, Chen Z, Chu N, Boeke JD, Cole PA. Bioorg Chem 62 64-73 (2015)
  38. Arginine-linked neomycin B dimers: synthesis, rRNA binding, and resistance enzyme activity. Jin Y, Watkins D, Degtyareva NN, Green KD, Spano MN, Garneau-Tsodikova S, Arya DP. Medchemcomm 7 164-169 (2016)
  39. Cj1123c (PglD), a multifaceted acetyltransferase from Campylobacter jejuni. Demendi M, Creuzenet C. Biochem Cell Biol 87 469-483 (2009)
  40. Insights into the Function of the N-Acetyltransferase SatA That Detoxifies Streptothricin in Bacillus subtilis and Bacillus anthracis. Burckhardt RM, Escalante-Semerena JC. Appl Environ Microbiol 85 e03029-18 (2019)
  41. Structure of Arabidopsis thaliana At1g77540 protein, a minimal acetyltransferase from the COG2388 family. Tyler RC, Bitto E, Berndsen CE, Bingman CA, Singh S, Lee MS, Wesenberg GE, Denu JM, Phillips GN, Markley JL. Biochemistry 45 14325-14336 (2006)
  42. Comprehensive analysis of protein acetyltransferases of human pathogen Mycobacterium tuberculosis. Xie L, Yang W, Fan X, Xie J. Biosci Rep 39 BSR20191661 (2019)
  43. Gcn5-Related N-Acetyltransferases (GNATs) With a Catalytic Serine Residue Can Play Ping-Pong Too. Baumgartner JT, Habeeb Mohammad TS, Czub MP, Majorek KA, Arolli X, Variot C, Anonick M, Minor W, Ballicora MA, Becker DP, Kuhn ML. Front Mol Biosci 8 646046 (2021)
  44. Structural and phylogenetic analyses of resistance to next-generation aminoglycosides conferred by AAC(2') enzymes. Bassenden AV, Dumalo L, Park J, Blanchet J, Maiti K, Arya DP, Berghuis AM. Sci Rep 11 11614 (2021)
  45. Uncovering the cytochrome P450-catalyzed methylenedioxy bridge formation in streptovaricins biosynthesis. Sun G, Hu C, Mei Q, Luo M, Chen X, Li Z, Liu Y, Deng Z, Zhang Z, Sun Y. Nat Commun 11 4501 (2020)
  46. In silico analysis and in vivo tests of the tuna dark muscle hydrolysate anti-oxidation effect. Han J, Tang S, Li Y, Bao W, Wan H, Lu C, Zhou J, Li Y, Cheong L, Su X. RSC Adv 8 14109-14119 (2018)
  47. Identification of amino acid residues essential for the yeast N-acetyltransferase Mpr1 activity by site-directed mutagenesis. Kotani T, Takagi H. FEMS Yeast Res 8 607-614 (2008)
  48. Structural basis of cofactor-mediated stabilization and substrate recognition of the α-tubulin acetyltransferase αTAT1. Yuzawa S, Kamakura S, Hayase J, Sumimoto H. Biochem J 467 103-113 (2015)
  49. Effect of solvent and protein dynamics in ligand recognition and inhibition of aminoglycoside adenyltransferase 2″-Ia. Bacot-Davis VR, Bassenden AV, Sprules T, Berghuis AM. Protein Sci 26 1852-1863 (2017)
  50. Plasticity of Aminoglycoside Binding to Antibiotic Kinase APH(2″)-Ia. Caldwell SJ, Berghuis AM. Antimicrob Agents Chemother 62 e00202-18 (2018)
  51. Small-Molecule Acetylation Controls the Degradation of Benzoate and Photosynthesis in Rhodopseudomonas palustris. VanDrisse CM, Escalante-Semerena JC. mBio 9 e01895-18 (2018)
  52. Characterization of the structure and catalytic activity of Legionella pneumophila VipF. Young BH, Caldwell TA, McKenzie AM, Kokhan O, Berndsen CE. Proteins 84 1422-1430 (2016)
  53. Molecular basis of antibiotic self-resistance in a bee larvae pathogen. Dang T, Loll B, Müller S, Skobalj R, Ebeling J, Bulatov T, Gensel S, Göbel J, Wahl MC, Genersch E, Mainz A, Süssmuth RD. Nat Commun 13 2349 (2022)
  54. Protocol for the development of coarse-grained structures for macromolecular simulation using GROMACS. Niranjan V, Rao P, Uttarkar A, Kumar J. PLoS One 18 e0288264 (2023)
  55. Thermodynamics of an aminoglycoside modifying enzyme with low substrate promiscuity: The aminoglycoside N3 acetyltransferase-VIa. Kumar P, Serpersu EH. Proteins 85 1258-1265 (2017)
  56. Crystallization and preliminary crystallographic analysis of hygromycin B phosphotransferase from Escherichia coli. Iino D, Takakura Y, Kuroiwa M, Kawakami R, Sasaki Y, Hoshino T, Ohsawa K, Nakamura A, Yajima S. Acta Crystallogr Sect F Struct Biol Cryst Commun 63 685-688 (2007)
  57. Mechanistic plasticity in ApmA enables aminoglycoside promiscuity for resistance. Bordeleau E, Stogios PJ, Evdokimova E, Koteva K, Savchenko A, Wright GD. Nat Chem Biol 20 234-242 (2024)
  58. Novel D-glutamate catabolic pathway in marine Proteobacteria and halophilic archaea. Yu Y, Wang P, Cao HY, Teng ZJ, Zhu Y, Wang M, McMinn A, Chen Y, Xiang H, Zhang YZ, Chen XL, Zhang YQ. ISME J 17 537-548 (2023)
  59. Withdrawn Infect Disord Drug Targets (2012)


Related citations provided by authors (1)