title: What can structure tell us about in vivo function? The case of aminoglycoside-resistance genes.
abstract: Resistance to antibiotics used in the treatment of bacterial infections is an expanding clinical problem. Aminoglycosides, one of the oldest classes of natural product antibiotics, exert their bactericidal effect as the result of inhibiting bacterial protein synthesis by binding to the acceptor site of the 30 S ribosomal subunit. The most common mechanism of clinical resistance to aminoglycosides results from the expression of enzymes that covalently modify the aminoglycoside. We will discuss the enzymology and structure of two representative chromosomally encoded aminoglycoside N-acetyltransferases, Mycobacterium tuberculosis AAC(2')-Ic and Salmonella enterica AAC(6')-Iy, and speculate about their possible physiological function and substrates.
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: M
authors.initials: M
authors.lastname: Vetting
authors.forename: S L
authors.initials: SL
authors.lastname: Roderick
authors.forename: S
authors.initials: S
authors.lastname: Hegde
authors.forename: S
authors.initials: S
authors.lastname: Magnet
authors.forename: J S
authors.initials: JS
authors.lastname: Blanchard
mesh_terms: D000123:Acetyltransferases / Q000737:chemistry / Q000235:genetics; D000617:Aminoglycosides / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002240:Carbohydrate Sequence; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004354:Drug Screening Assays, Antitumor; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics; D011487:Protein Conformation
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000123:Acetyltransferases; C443113:aminoglycoside 2'-N-acetyltransferase