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X射线晶体学揭示的辛可宁与抗菌靶标酶MurA的异常结合模式。

The unusual binding mode of cnicin to the antibacterial target enzyme MurA revealed by X-ray crystallography.

作者信息

Steinbach Anke, Scheidig Axel J, Klein Christian D

机构信息

Pharmazeutische Chemie, Universität Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany.

出版信息

J Med Chem. 2008 Aug 28;51(16):5143-7. doi: 10.1021/jm800609p. Epub 2008 Aug 1.

DOI:10.1021/jm800609p
PMID:18672863
Abstract

We present the X-ray structure of the antibacterial target enzyme MurA in complex with its substrate UNAG and the sesquiterpene lactone cnicin, a potent inhibitor of the enzyme. The structure reveals that MurA has catalyzed the formation of a covalent adduct between cnicin and UNAG. This adduct, which can be regarded as a noncovalent suicide inhibitor, has been formed by an unusual "anti-Michael" 1,3-addition of UNAG to an alpha,beta-unsaturated carbonyl function in cnicin.

摘要

我们展示了抗菌靶标酶MurA与底物UNAG以及倍半萜内酯土木香内酯（该酶的一种有效抑制剂）形成复合物的X射线结构。该结构表明，MurA催化了土木香内酯与UNAG之间共价加合物的形成。这种加合物可被视为一种非共价自杀抑制剂，它是通过UNAG以一种不寻常的“反迈克尔”1,3-加成方式加成到土木香内酯中的α,β-不饱和羰基官能团上而形成的。

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