Open AccessStructure of the extended‐spectrum class C β‐lactamase ADC‐1 from Acinetobacter baumannii
Author(s) -
Bhattacharya Monolekha,
Toth Marta,
Antunes Nuno Tiago,
Smith Clyde A.,
Vakulenko Sergei B.
Publication year - 2014
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
ISSN - 1399-0047
DOI - 10.1107/s1399004713033014
Subject(s) - acinetobacter baumannii , cephalosporin , enzyme , antibiotics , microbiology and biotechnology , acinetobacter , broad spectrum , gene , antibiotic resistance , bacteria , biology , chemistry , genetics , combinatorial chemistry , biochemistry , pseudomonas aeruginosa
ADC‐type class C β‐lactamases comprise a large group of enzymes that are encoded by genes located on the chromosome of Acinetobacter baumannii , a causative agent of serious bacterial infections. Overexpression of these enzymes renders A. baumannii resistant to various β‐lactam antibiotics and thus severely compromises the ability to treat infections caused by this deadly pathogen. Here, the high‐resolution crystal structure of ADC‐1, the first member of this clinically important family of antibiotic‐resistant enzymes, is reported. Unlike the narrow‐spectrum class C β‐lactamases, ADC‐1 is capable of producing resistance to the expanded‐spectrum cephalosporins, rendering them inactive against A. baumannii . The extension of the substrate profile of the enzyme is likely to be the result of structural differences in the R2‐loop, primarily the deletion of three residues and subsequent rearrangement of the A10a and A10b helices. These structural rearrangements result in the enlargement of the R2 pocket of ADC‐1, allowing it to accommodate the bulky R2 substituents of the third‐generation cephalosporins, thus enhancing the catalytic efficiency of the enzyme against these clinically important antibiotics.