3HBR

Crystal structure of OXA-48 beta-lactamase

3HBR の概要

• エントリーDOI: 10.2210/pdb3hbr/pdb
• 分子名称: OXA-48, 1,2-ETHANEDIOL (3 entities in total)
• 機能のキーワード: class d beta-lactamase, oxa-48, antibiotic, dimer, hydrolase
• 由来する生物種: Klebsiella pneumoniae
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 122007.17

構造登録者

Calderone, V.,Mangani, S.,Benvenuti, M.,Rossolini, G.M.,Docquier, J.D. (登録日: 2009-05-05, 公開日: 2009-06-23, 最終更新日: 2023-11-22)

主引用文献

Docquier, J.D.,Calderone, V.,De Luca, F.,Benvenuti, M.,Giuliani, F.,Bellucci, L.,Tafi, A.,Nordmann, P.,Botta, M.,Rossolini, G.M.,Mangani, S.
Crystal structure of the OXA-48 beta-lactamase reveals mechanistic diversity among class D carbapenemases.
Chem.Biol., 16:540-547, 2009

PubMed Abstract: Carbapenem-hydrolyzing class D beta-lactamases (CHDLs) are enzymes found in important Gram-negative pathogens (mainly Acinetobacter baumannii and Enterobacteriaceae) that confer resistance to beta-lactam antibiotics, and notably carbapenems. The crystal structure of the OXA-48 carbapenemase was determined at pH 7.5 and at a resolution of 1.9 A. Surprisingly, and by contrast with OXA-24, the only other CHDL of known crystal structure, the structure of OXA-48 was similar to OXA-10, an enzyme devoid of carbapenemase activity, indicating that the hydrolysis of these compounds could depend on subtle changes in the active site region. Moreover, the active site groove of OXA-48 was different from that of OXA-24 in shape, dimensions, and charge distribution. Molecular dynamics pointed to the functional relevance of residues located in or close to the beta5-beta6 loop and allowed us to propose a mechanism for carbapenem hydrolysis by OXA-48.

PubMed: 19477418
DOI: 10.1016/j.chembiol.2009.04.010

実験手法

X-RAY DIFFRACTION (1.9 Å)