4NET

Crystal structure of ADC-1 beta-lactamase

4NET の概要

• エントリーDOI: 10.2210/pdb4net/pdb
• 分子名称: AmpC, NITRATE ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: beta-lactamase, antibiotic resistance, apo enzyme, hydrolase
• 由来する生物種: Acinetobacter baumannii
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 81883.22

構造登録者

Bhattacharya, M.,Toth, M.,Antunes, N.T.,Smith, C.A.,Vakulenko, S.B. (登録日: 2013-10-30, 公開日: 2014-03-12, 最終更新日: 2024-02-28)

主引用文献

Bhattacharya, M.,Toth, M.,Antunes, N.T.,Smith, C.A.,Vakulenko, S.B.
Structure of the extended-spectrum class C beta-lactamase ADC-1 from Acinetobacter baumannii.
Acta Crystallogr.,Sect.D, 70:760-771, 2014

PubMed Abstract: 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.

PubMed: 24598745
DOI: 10.1107/S1399004713033014

実験手法

X-RAY DIFFRACTION (1.2 Å)