2QDS

Crystal Structure of the Zinc Carbapenemase CPHA in Complex with the Inhibitor D-Captopril

2QDS の概要

• エントリーDOI: 10.2210/pdb2qds/pdb
• 関連するPDBエントリー: 1X8G 1X8I 2GKL
• 分子名称: Beta-lactamase, ZINC ION, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: hydrolase, lactamase, inhibitor, zn
• 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: 26071.95

構造登録者

Garau, G.,Dideberg, O. (登録日: 2007-06-21, 公開日: 2007-07-17, 最終更新日: 2023-08-30)

主引用文献

Lienard, B.M.,Garau, G.,Horsfall, L.,Karsisiotis, A.I.,Damblon, C.,Lassaux, P.,Papamicael, C.,Roberts, G.C.,Galleni, M.,Dideberg, O.,Frere, J.M.,Schofield, C.J.
Structural basis for the broad-spectrum inhibition of metallo-beta-lactamases by thiols.
Org.Biomol.Chem., 6:2282-2294, 2008

PubMed Abstract: The development of broad-spectrum metallo-beta-lactamase (MBL) inhibitors is challenging due to structural diversity and differences in metal utilisation by these enzymes. Analysis of structural data, followed by non-denturing mass spectrometric analyses, identified thiols proposed to inhibit representative MBLs from all three sub-classes: B1, B2 and B3. Solution analyses led to the identification of broad spectrum inhibitors, including potent inhibitors of the CphA MBL (Aeromonas hydrophila). Structural studies revealed that, as observed for other B1 and B3 MBLs, inhibition of the L1 MBL thiols involves metal chelation. Evidence is reported that this is not the case for inhibition of the CphA enzyme by some thiols; the crystal structure of the CphA-Zn-inhibitor complex reveals a binding mode in which the thiol does not interact with the zinc. The structural data enabled the design and the production of further more potent inhibitors. Overall the results suggest that the development of reasonably broad-spectrum MBL inhibitors should be possible.

PubMed: 18563261
DOI: 10.1039/b802311e

実験手法

X-RAY DIFFRACTION (1.66 Å)