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Publication Abstract from PubMed

ADC-type class C beta-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 beta-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 beta-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.

Structure of the extended-spectrum class C beta-lactamase ADC-1 from Acinetobacter baumannii.,Bhattacharya M, Toth M, Antunes NT, Smith CA, Vakulenko SB Acta Crystallogr D Biol Crystallogr. 2014 Mar;70(Pt 3):760-71. doi:, 10.1107/S1399004713033014. Epub 2014 Feb 22. PMID:24598745^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.