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PMID:9702193
| Citation |
Bussiere, DE, Pratt, SD, Katz, L, Severin, JM, Holzman, T and Park, CH (1998) The structure of VanX reveals a novel amino-dipeptidase involved in mediating transposon-based vancomycin resistance. Mol. Cell 2:75-84 |
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| 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. |
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| Keywords |
Alanine/metabolism; Amino Acid Sequence; Animals; Bacterial Proteins/antagonists & inhibitors; Bacterial Proteins/chemistry; Binding Sites; Carboxypeptidases/chemistry; Copper/pharmacology; Crystallography, X-Ray; DNA Transposable Elements/genetics; Dipeptidases/antagonists & inhibitors; Dipeptidases/chemistry; Dipeptides/metabolism; Drug Resistance, Microbial/genetics; Enterococcus faecium/enzymology; Enzyme Inhibitors/pharmacology; Hedgehog Proteins; Mice; Models, Molecular; Molecular Sequence Data; Organophosphorus Compounds/pharmacology; Propionates/pharmacology; Protein Conformation; Proteins/chemistry; Sequence Alignment; Sequence Homology, Amino Acid; Serine-Type D-Ala-D-Ala Carboxypeptidase; Structure-Activity Relationship; Trans-Activators; Vancomycin/pharmacology |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
Contributes to |
GO:0016805: dipeptidase activity |
ECO:0000255: |
UniProtKB:Q06241
|
F |
It is inferred that the protein VanX has dipeptidase properties based on it's similarities in structure to the known murine Sonic Hedgehog (an N-terminal fragment composing the hydrolytic functionality) and the D-ala-D-ala-carboxypeptidase S.Albus(composing the peptidase functionality). Fig 6A shows the alignment comparison of all three; VanX and MSH overlap for 92 alpha carbons, and VanX and S.Albus overlap for 114 alpha carbons. 6B shows at least 7 major homologous overlaps between VanX, MSH and S.Albus. In 6A, the superfamily relationship amongst VanX, MSH and S.Albus is validated by the similarities in active site location;in VanX it is located within residues 83-111, which aligns almost exact with MSH and S.Albus. |
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Notes
See also
References
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