2WKE

Crystal structure of the Actinomadura R39 DD-peptidase inhibited by 6- beta-iodopenicillanate.

2WKE の概要

• エントリーDOI: 10.2210/pdb2wke/pdb
• 関連するPDBエントリー: 1W79 1W8Q 1W8Y 2VGJ 2VGK 2WIX
• 分子名称: D-ALANYL-D-ALANINE CARBOXYPEPTIDASE, (3S)-2,2-dimethyl-3,4-dihydro-2H-1,4-thiazine-3,6-dicarboxylic acid, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: hydrolase, antibiotic resistance, actinomadura, penicillin binding, iodopenicillanate
• 由来する生物種: ACTINOMADURA SP.
• 細胞内の位置: Secreted: P39045
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 194203.31

構造登録者

Sauvage, E.,Herman, R.,Kerff, F.,Charlier, P. (登録日: 2009-06-10, 公開日: 2009-12-01, 最終更新日: 2024-11-20)

主引用文献

Sauvage, E.,Zervosen, A.,Dive, G.,Herman, R.,Amoroso, A.,Joris, B.,Fonze, E.,Pratt, R.F.,Luxen, A.,Charlier, P.,Kerff, F.
Structural Basis of the Inhibition of Class a Beta-Lactamases and Penicillin-Binding Proteins by 6-Beta-Iodopenicillanate.
J.Am.Chem.Soc., 131:15262-, 2009

PubMed Abstract: 6-Beta-halogenopenicillanates are powerful, irreversible inhibitors of various beta-lactamases and penicillin-binding proteins. Upon acylation of these enzymes, the inhibitors are thought to undergo a structural rearrangement associated with the departure of the iodide and formation of a dihydrothiazine ring, but, to date, no structural evidence has proven this. 6-Beta-iodopenicillanic acid (BIP) is shown here to be an active antibiotic against various bacterial strains and an effective inhibitor of the class A beta-lactamase of Bacillus subtilis BS3 (BS3) and the D,D-peptidase of Actinomadura R39 (R39). Crystals of BS3 and of R39 were soaked with a solution of BIP and their structures solved at 1.65 and 2.2 A, respectively. The beta-lactam and the thiazolidine rings of BIP are indeed found to be fused into a dihydrothiazine ring that can adopt two stable conformations at these active sites. The rearranged BIP is observed in one conformation in the BS3 active site and in two monomers of the asymmetric unit of R39, and is observed in the other conformation in the other two monomers of the asymmetric unit of R39. The BS3 structure reveals a new mode of carboxylate interaction with a class A beta-lactamase active site that should be of interest in future inhibitor design.

PubMed: 19919161
DOI: 10.1021/JA9051526

実験手法

X-RAY DIFFRACTION (2.2 Å)