Abstract
ADC-56, a novel extended-spectrum AmpC (ESAC) β-lactamase, was identified in an Acinetobacter baumannii clinical isolate. ADC-56 possessed an R148Q change compared with its putative progenitor, ADC-30, which enabled it to hydrolyze cefepime. Molecular modeling suggested that R148 interacted with Q267, E272, and I291 through a hydrogen bond network which constrained the H-10 helix. This permitted cefepime to undergo conformational changes in the active site, with the carboxyl interacting with R340, likely allowing for better binding and turnover.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Acinetobacter baumannii / drug effects*
-
Acinetobacter baumannii / enzymology*
-
Acinetobacter baumannii / genetics
-
Anti-Bacterial Agents / pharmacology
-
Bacterial Proteins / genetics*
-
Cefepime
-
Cephalosporin Resistance / genetics
-
Cephalosporinase / chemistry
-
Cephalosporinase / genetics
-
Cephalosporinase / metabolism*
-
Cephalosporins / pharmacology*
-
Drug Resistance, Bacterial
-
Genes, Bacterial
-
Microbial Sensitivity Tests
-
Molecular Sequence Data
-
beta-Lactamases / genetics*
Substances
-
Anti-Bacterial Agents
-
Bacterial Proteins
-
Cephalosporins
-
Cefepime
-
Cephalosporinase
-
AmpC beta-lactamases
-
beta-Lactamases
Associated data
-
GDB/JF265067
-
GENBANK/JF265068