The structure of VanX reveals a novel amino-dipeptidase involved in mediating transposon-based vancomycin resistance

被引：71

作者：

Bussiere, DE

Pratt, SD

Katz, L

Severin, JM

Holzman, T

Park, CH

机构：

[1] Abbott Labs, Div Pharmaceut Prod, Lab Prot Crystallog, Abbott Pk, IL 60064 USA

[2] Abbott Labs, Div Pharmaceut Prod, Prot Biochem Grp, Abbott Pk, IL 60064 USA

[3] Abbott Labs, Div Pharmaceut Prod, Div Sci Informat Anal & Managment, Abbott Pk, IL 60064 USA

来源：

MOLECULAR CELL | 1998年 / 2卷 / 01期

关键词：

D O I：

10.1016/S1097-2765(00)80115-X

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

VanX is a zinc-dependent D-alanyl-D-alanine dipeptidase that is a critical component in a system that mediates transposon-based vancomycin resistance in enterococci. It is also a key drug target in circumventing clinical vancomycin resistance. The structure of VanX from E. faecium has been solved by X-ray crystallography and reveals a Zn2+-dipeptidase with a unique overall fold and a well-defined active site confined within a cavity of limited size. The crystal structures of VanX, the VanX:D-alanyl-D-alanine complex, the VanX:D-alanine complex, and VanX in complex with phosphonate and phosphinate transition-state analog inhibitors, are also presented at high resolution. Structural homology searches of known structures revealed that the fold of VanX is similar to those of two proteins: the N-terminal fragment of murine Sonic hedgehog and the Zn2+-dependent N-acyl-D-alanyl-D-alanine carboxypeptidase of S. albus G.

引用

页码：75 / 84

页数：10

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[41] Delocalizing trypsin specificity with metal activation [J].