ArticleBiochemistry2008
Mechanistic and structural analysis of aminoglycoside N-acetyltransferase AAC(6')-Ib and its bifunctional, fluoroquinolone-active AAC(6')-Ib-cr variant.
Article in Biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 143 citations in OpenAlex.
- Systematic review: genotypic and phenotypic resistance of fluoroquinolone-resistantFrontiers in veterinary science · 2025Pooled it
- Molecular and Computational Insights of Novel Mutations in Aminoglycoside-Modifying Genes of P. aeruginosa.Molecular biotechnology · 2026Article
- Heteroresistance to amikacin inMicrobiology spectrum · 2026Article
- Acquired resistance in Stenotrophomonas maltophilia: Mechanisms underlying the shift from multidrug to pandrug resistance.European journal of microbiology & immunology · 2026Review
- Profiling of Antimicrobial Resistance Genes and Genotype-Phenotype Associations inInternational journal of food science · 2026Article
- Large-scale comparative genomics and structure-function analysis enables characterization of known and novel genetic determinants of antimicrobial resistance in bacterial pathogens.Frontiers in microbiology · 2026Article
- Identification and Characterization of the Biosynthesis of the Hybrid NRPS-NIS Siderophore Nocardichelin.ACS chemical biology · 2025Article
- Carbapenem Resistant Serratia marcescens Harboring blaCurrent microbiology · 2025Article
- Molecular epidemiology of Escherichia coli in bloodstream infections from a general hospital in Ningxia, China, 2022-2023.BMC infectious diseases · 2025Article
- Mechanisms of fluoroquinolone resistance among Escherichia coli isolates from urinary tract infections in Thailand.PloS one · 2025Article
- Three simple and cost-effective assays for AAC(6')-Ib-cr enzyme activity.Frontiers in microbiology · 2025Article
- Article
- Prevalence of plasmid-mediated quinolone resistance genes in extended-spectrum beta-lactamase producingHeliyon · 2024Article
- Structure-Activity Relationship of Pyrrolidine Pentamine Derivatives as Inhibitors of the Aminoglycoside 6'-Antibiotics (Basel, Switzerland) · 2024Article
- The Peptide Antibiotic Corramycin Adopts a β-Hairpin-like Structure and Is Inactivated by the Kinase ComG.Journal of the American Chemical Society · 2024Article
- Article
- Bacterial protein acetylation: mechanisms, functions, and methods for study.Frontiers in cellular and infection microbiology · 2024Review
- Novel D-glutamate catabolic pathway in marine Proteobacteria and halophilic archaea.The ISME journal · 2023Article
- Characterization of Proteus mirabilis and associated plasmids isolated from anaerobic dairy cattle manure digesters.PloS one · 2023Article
- Quinolone Antibiotics: Resistance and Therapy.Infection and drug resistance · 2023Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Enzymatic modification of aminoglycoside antibiotics mediated by regioselective aminoglycoside N-acetyltransferases is the predominant cause of bacterial resistance to aminoglycosides. A recently discovered bifunctional aminoglycoside acetyltransferase (AAC(6')-Ib variant, AAC(6')-Ib-cr) has been shown to catalyze the acetylation of fluoroquinolones as well as aminoglycosides. We have expressed and purified AAC(6')-Ib-wt and its bifunctional variant AAC(6')-Ib-cr in Escherichia coli and characterized their kinetic and chemical mechanism. Initial velocity and dead-end inhibition studies support an ordered sequential mechanism for the enzyme(s). The three-dimensional structure of AAC(6')-Ib-wt was determined in various complexes with donor and acceptor ligands to resolutions greater than 2.2 A. Observation of the direct, and optimally positioned, interaction between the 6'-NH 2 and Asp115 suggests that Asp115 acts as a general base to accept a proton in the reaction. The structure of AAC(6')-Ib-wt permits the construction of a molecular model of the interactions of fluoroquinolones with the AAC(6')-Ib-cr variant. The model suggests that a major contribution to the fluoroquinolone acetylation activity comes from the Asp179Tyr mutation, where Tyr179 makes pi-stacking interactions with the quinolone ring facilitating quinolone binding. The model also suggests that fluoroquinolones and aminoglycosides have different binding modes. On the basis of kinetic properties, the pH dependence of the kinetic parameters, and structural information, we propose an acid/base-assisted reaction catalyzed by AAC(6')-Ib-wt and the AAC(6')-Ib-cr variant involving a ternary complex.
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