EC 3.4.13.22 - D-Ala-D-Ala dipeptidase

  IntEnz view ENZYME view

IntEnz Enzyme Nomenclature
EC 3.4.13.22

Names

Accepted name:
D-Ala-D-Ala dipeptidase
Other names:
D-alanyl-D-alanine dipeptidase
vanX D-Ala-D-Ala dipeptidase
VanX
Systematic name:
-

Reaction

Cofactor

Comments:

A Zn2+-dependent enzyme [4]. The enzyme protects Enterococcus faecium from the antibiotic vancomycin, which can bind to the -D-Ala-D-Ala sequence at the C-terminus of the peptidoglycan pentapeptide (see diagram). This enzyme reduces the availability of the free dipeptide D-Ala-D-Ala, which is the precursor for this pentapeptide sequence, allowing D-Ala-(R)-lactate (for which vancomycin has much less affinity) to be added to the cell wall instead [2,3]. The enzyme is stereospecific, as L-Ala-L-Ala, D-Ala-L-Ala and L-Ala-D-Ala are not substrates [2]. Belongs in peptidase family M15.

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , DIAGRAM , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , MEROPS , UniPathway
Structural data: CSA , EC2PDB
UniProtKB/Swiss-Prot:

References

  1. Reynolds, P.E., Depardieu, F., Dutka-Malen, S., Arthur, M. and Courvalin, P.
    Glycopeptide resistance mediated by enterococcal transposon Tn1546 requires production of VanX for hydrolysis of D-alanyl-D-alanine.
    Mol. Microbiol. 13: 1065-1070 (1994). [PMID: 7854121]
  2. Wu, Z., Wright, G.D and, Walsh, C.T.
    Overexpression, purification, and characterization of VanX, a D-, D-dipeptidase which is essential for vancomycin resistance in Enterococcus faecium BM4147.
    Biochemistry 34: 2455-2463 (1995). [PMID: 7873524]
  3. McCafferty, D.G., Lessard, I.A.D. and Walsh, C.T.
    Mutational analysis of potential zinc-binding residues in the active site of the enterococcal D-Ala-D-Ala dipeptidase VanX.
    Biochemistry 36: 10498-10505 (1997). [PMID: 9265630]
  4. Bussiere, D.E., Pratt, S.D., Katz, L., Severin, J.M., Holzman, T. and Park, C.H.
    The structure of VanX reveals a novel amino-dipeptidase involved in mediating transposon-based vancomycin resistance.
    Mol. Cell 2: 75-84 (1998). [PMID: 9702193]
  5. Tan, A.L., Loke, P. and Sim, T.S.
    Molecular cloning and functional characterisation of VanX, a D-alanyl-D-alanine dipeptidase from Streptomyces coelicolor A3(2).
    Res. Microbiol. 153: 27-32 (2002). [PMID: 11881895]
  6. Matthews, M.L., Periyannan, G., Hajdin, C., Sidgel, T.K., Bennett, B. and Crowder, M.W.
    Probing the reaction mechanism of the D-ala-D-ala dipeptidase, VanX, by using stopped-flow kinetic and rapid-freeze quench EPR studies on the Co(II)-substituted enzyme.
    J. Am. Chem. Soc. 128: 13050-13051 (2006). [PMID: 17017774]

[EC 3.4.13.22 created 2006]