1BC2

ZN-DEPENDENT METALLO-BETA-LACTAMASE FROM BACILLUS CEREUS

1BC2 の概要

• エントリーDOI: 10.2210/pdb1bc2/pdb
• 分子名称: METALLO-BETA-LACTAMASE II, ZINC ION, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: hydrolase, metallo beta-lactamase, penicillinase, antibiotic resistance
• 由来する生物種: Bacillus cereus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 50444.83

構造登録者

Fabiane, S.M.,Sutton, B.J. (登録日: 1997-04-11, 公開日: 1998-10-14, 最終更新日: 2024-02-07)

主引用文献

Fabiane, S.M.,Sohi, M.K.,Wan, T.,Payne, D.J.,Bateson, J.H.,Mitchell, T.,Sutton, B.J.
Crystal structure of the zinc-dependent beta-lactamase from Bacillus cereus at 1.9 A resolution: binuclear active site with features of a mononuclear enzyme.
Biochemistry, 37:12404-12411, 1998

PubMed Abstract: The structure of the zinc-dependent beta-lactamase II from Bacillus cereus has been determined at 1.9 A resolution in a crystal form with two molecules in the asymmetric unit and 400 waters (space group P3121; Rcryst = 20.8%). The active site contains two zinc ions: Zn1 is tightly coordinated by His86, His88, and His149, while Zn2 is loosely coordinated by Asp90, Cys168, and His210. A water molecule (W1) lies between the two zinc ions but is significantly closer to Zn1 and at a distance of only 1.9 A is effectively a hydroxide moiety and a potential, preactivated nucleophile. In fact, Asp90 bridges W1 to Zn2, and its location is thus distinct from that of the bridging water molecules in the binuclear zinc peptidases or other binuclear zinc hydrolases. Modeling of penicillin, cephalosporin, and carbapenem binding shows that all are readily accommodated within the shallow active site cleft of the enzyme, and the Zn1-bound hydroxide is ideally located for nucleophilic attack at the beta-lactam carbonyl. This enzyme also functions with only one zinc ion present. The Zn1-Zn2 distances differ in the two independent molecules in the crystal (3.9 and 4.4 A), yet the Zn1-W1 distances are both 1.9 A, arguing against involvement of Zn2 in W1 activation. The role of Zn2 is unclear, but the B. cereus enzyme may be an evolutionary intermediate between the mono- and bizinc metallo-beta-lactamases. The broad specificity of this enzyme, together with the increasing prevalence of zinc-dependent metallo-beta-lactamases, poses a real clinical threat, and this structure provides a basis for understanding its mechanism and designing inhibitors.

PubMed: 9730812
DOI: 10.1021/bi980506i

実験手法

X-RAY DIFFRACTION (1.9 Å)