3FAI

The Di Zinc Carbapenemase CphA N220G mutant

3FAI の概要

• エントリーDOI: 10.2210/pdb3fai/pdb
• 関連するPDBエントリー: 1X8G 1X8H 1X8I 2GKL 2QDS 3F9O
• 分子名称: Beta-lactamase, ZINC ION, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: hydrolase, antibiotic resistance, metal-binding
• 由来する生物種: Aeromonas hydrophila
• 細胞内の位置: Periplasm (Probable): P26918
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26556.89

構造登録者

Delbruck, H.,Hoffmann, K.M.V. (登録日: 2008-11-17, 公開日: 2009-09-01, 最終更新日: 2023-11-01)

主引用文献

Bebrone, C.,Delbruck, H.,Kupper, M.B.,Schlomer, P.,Willmann, C.,Frere, J.-M.,Fischer, R.,Galleni, M.,Hoffmann, K.M.V.
The structure of the dizinc subclass B2 metallo-beta-lactamase CphA reveals that the second inhibitory zinc ion binds in the histidine site
Antimicrob.Agents Chemother., 53:4464-4471, 2009

PubMed Abstract: Bacteria can defend themselves against beta-lactam antibiotics through the expression of class B beta-lactamases, which cleave the beta-lactam amide bond and render the molecule harmless. There are three subclasses of class B beta-lactamases (B1, B2, and B3), all of which require Zn2+ for activity and can bind either one or two zinc ions. Whereas the B1 and B3 metallo-beta-lactamases are most active as dizinc enzymes, subclass B2 enzymes, such as Aeromonas hydrophila CphA, are inhibited by the binding of a second zinc ion. We crystallized A. hydrophila CphA in order to determine the binding site of the inhibitory zinc ion. X-ray data from zinc-saturated crystals allowed us to solve the crystal structures of the dizinc forms of the wild-type enzyme and N220G mutant. The first zinc ion binds in the cysteine site, as previously determined for the monozinc form of the enzyme. The second zinc ion occupies a slightly modified histidine site, where the conserved His118 and His196 residues act as metal ligands. This atypical coordination sphere probably explains the rather high dissociation constant for the second zinc ion compared to those observed with enzymes of subclasses B1 and B3. Inhibition by the second zinc ion results from immobilization of the catalytically important His118 and His196 residues, as well as the folding of the Gly232-Asn233 loop into a position that covers the active site.

PubMed: 19651913
DOI: 10.1128/AAC.00288-09

実験手法

X-RAY DIFFRACTION (1.7 Å)