Crystal structures of Staphylococcus aureus methionine aminopeptidase complexed with keto heterocycle and aminoketone inhibitors reveal the formation of a tetrahedral intermediate

被引：43

作者：

Douangamath, A ^{[1
]}

Dale, GE ^{[1
]}

D'Arcy, A ^{[1
]}

Almstetter, M ^{[1
]}

Eckl, R ^{[1
]}

Frutos-Hoener, A ^{[1
]}

Henkel, B ^{[1
]}

Illgen, K ^{[1
]}

Nerdinger, S ^{[1
]}

Schulz, H ^{[1
]}

MacSweeney, A ^{[1
]}

Thormann, M ^{[1
]}

Treml, A ^{[1
]}

Pierau, S ^{[1
]}

Wadman, S ^{[1
]}

Oefner, C ^{[1
]}

机构：

[1] Morphochem AG, CH-4058 Basel, Switzerland

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 06期

关键词：

D O I：

10.1021/jm034188j

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

High-resolution crystal structures of Staphylococcus aureus methionine aminopeptidase I in complex with various keto heterocycles and aminoketones were determined, and the intermolecular ligand interactions with the enzyme are reported. The compounds are effective inhibitors of the S. aureus enzyme because of the formation of an uncleavable tetrahedral intermediate upon binding. The electron densities unequivocally show the enzyme-catalyzed transition-state analogue mimicking that for amide bond hydrolysis of substrates.

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页码：1325 / 1328

页数：4

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