2NZF

Structure of beta-lactamase II from Bacillus cereus. R121H, C221S double mutant. Space group C2.

2NZF の概要

• エントリーDOI: 10.2210/pdb2nzf/pdb
• 分子名称: Beta-lactamase II, ZINC ION (3 entities in total)
• 機能のキーワード: beta-lactamase ii, bacillus cereus, hydrolase
• 由来する生物種: Bacillus cereus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24324.02

構造登録者

Medrano Martin, F.J.,Vila, A.J.,Gonzalez, J.M. (登録日: 2006-11-23, 公開日: 2007-05-29, 最終更新日: 2023-08-30)

主引用文献

Gonzalez, J.M.,Medrano Martin, F.J.,Costello, A.L.,Tierney, D.L.,Vila, A.J.
The Zn2 position in metallo-beta-lactamases is critical for activity: a study on chimeric metal sites on a conserved protein scaffold.
J.Mol.Biol., 373:1141-1156, 2007

PubMed Abstract: Metallo-beta-lactamases (MbetaLs) are bacterial Zn(II)-dependent hydrolases that confer broad-spectrum resistance to beta-lactam antibiotics. These enzymes can be subdivided into three subclasses (B1, B2 and B3) that differ in their metal binding sites and their characteristic tertiary structure. To date there are no clinically useful pan-MbetaL inhibitors available, mainly due to the unawareness of key catalytic features common to all MbetaL brands. Here we have designed, expressed and characterized two double mutants of BcII, a di-Zn(II) B1-MbetaL from Bacillus cereus, namely BcII-R121H/C221D (BcII-HD) and BcII-R121H/C221S (BcII-HS). These mutants display modified environments at the so-called Zn2 site or DCH site, reproducing the metal coordination environments of structurally related metallohydrolases. Through a combination of structural and functional studies, we found that BcII-HD is an impaired beta-lactamase even as a di-Zn(II) enzyme, whereas BcII-HS exhibits the ability to exist as mono or di-Zn(II) species in solution, with different catalytic performances. We show that these effects result from an altered position of Zn2, which is incapable of providing a productive interaction with the substrate beta-lactam ring. These results indicate that the position of Zn2 is essential for a productive substrate binding and hydrolysis.

PubMed: 17915249
DOI: 10.1016/j.jmb.2007.08.031
主引用文献が同じPDBエントリー

実験手法

X-RAY DIFFRACTION (2.28 Å)