4Y0T

Crystal structure of apo form of OXA-58, a Carbapenem hydrolyzing Class D beta-lactamase from Acinetobacter baumanii (P21, 4mol/ASU)

4Y0T の概要

• エントリーDOI: 10.2210/pdb4y0t/pdb
• 関連するPDBエントリー: 4Y0O 4Y0U
• 分子名称: Beta-lactamase (2 entities in total)
• 機能のキーワード: class d beta-lactamase, oxa-58, 4mol/asu, hydrolase
• 由来する生物種: Acinetobacter baumannii
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 125992.84

構造登録者

Pratap, S.,Katiki, M.,Gill, P.,Golemi-Kotra, D.,Kumar, P. (登録日: 2015-02-06, 公開日: 2016-01-13, 最終更新日: 2025-04-09)

主引用文献

Pratap, S.,Katiki, M.,Gill, P.,Kumar, P.,Golemi-Kotra, D.
Active-Site Plasticity Is Essential to Carbapenem Hydrolysis by OXA-58 Class D beta-Lactamase of Acinetobacter baumannii.
Antimicrob.Agents Chemother., 60:75-86, 2015

PubMed Abstract: Carbapenem-hydrolyzing class D β-lactamases (CHDLs) are a subgroup of class D β-lactamases, which are enzymes that hydrolyze β-lactams. They have attracted interest due to the emergence of multidrug-resistant Acinetobacter baumannii, which is not responsive to treatment with carbapenems, the usual antibiotics of choice for this bacterium. Unlike other class D β-lactamases, these enzymes efficiently hydrolyze carbapenem antibiotics. To explore the structural requirements for the catalysis of carbapenems by these enzymes, we determined the crystal structure of the OXA-58 CHDL of A. baumannii following acylation of its active-site serine by a 6α-hydroxymethyl penicillin derivative that is a structural mimetic for a carbapenem. In addition, several point mutation variants of the active site of OXA-58, as identified by the crystal structure analysis, were characterized kinetically. These combined studies confirm the mechanistic relevance of a hydrophobic bridge formed over the active site. This structural feature is suggested to stabilize the hydrolysis-productive acyl-enzyme species formed from the carbapenem substrates of this enzyme. Furthermore, our structural studies provide strong evidence that the hydroxyethyl group of carbapenems samples different orientations in the active sites of CHDLs, and the optimum orientation for catalysis depends on the topology of the active site allowing proper closure of the active site. We propose that CHDLs use the plasticity of the active site to drive the mechanism of carbapenem hydrolysis toward efficiency.

PubMed: 26459904
DOI: 10.1128/AAC.01393-15

実験手法

X-RAY DIFFRACTION (2.3 Å)