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Mol Cell. 1998 Jul;2(1):75-84.

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

Author information

1
Laboratory of Protein Crystallography, Abbott Laboratories, Illinois 60064, USA. bussierd@tvsfrank.pprd.abbott.com

Abstract

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 Zn(2+)-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 Zn(2+)-dependent N-acyl-D-alanyl-D-alanine carboxypeptidase of S. albus G.

PMID:
9702193
[Indexed for MEDLINE]
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