Mechanistic and structural analysis of aminoglycoside N-acetyltransferase AAC(6')-Ib and its bifunctional, fluoroquinolone-active AAC(6')-Ib-cr variant.
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AAC(6')-Ib is a regioselective aminoglycoside N-acetyltransferase; such enzymes are the predominant cause of bacterial aminoglycoside resistance. It acetylates the 6'-amino group, with Asp115 acting as the general base.
"Enzymatic modification of aminoglycoside antibiotics mediated by regioselective aminoglycoside N-acetyltransferases is the predominant cause of bacterial resistance to aminoglycosides."
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AAC(6')-Ib-wt was expressed and purified as a soluble protein and its three-dimensional structure solved in complex with donor (CoA) and acceptor (aminoglycoside) ligands, defining the catalytic mechanism.
"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"
Fluoroquinolone-modifying enzyme: a new adaptation of a common aminoglycoside acetyltransferase.
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A variant of AAC(6')-Ib (AAC(6')-Ib-cr, bearing Trp102Arg and Asp179Tyr) acquires the ability to N-acetylate fluoroquinolones (ciprofloxacin), reducing their activity.
"ciprofloxacin in clinical bacterial isolates conferred by a variant of the gene encoding aminoglycoside acetyltransferase AAC(6')-Ib"
Gene Ontology annotation through association of InterPro records with GO terms
Gene Ontology annotation based on Enzyme Commission mapping
Gene Ontology annotation by UniProt keywords
Electronic Gene Ontology annotations created by ARBA machine learning models