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PMID:1998664
| Citation |
Bugg, TD, Dutka-Malen, S, Arthur, M, Courvalin, P and Walsh, CT (1991) Identification of vancomycin resistance protein VanA as a D-alanine:D-alanine ligase of altered substrate specificity. Biochemistry 30:2017-21 |
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| Abstract |
High-level glycopeptide resistance in Enterococcus faecium BM4147 is mediated by a 38-kDa protein VanA, whose amino acid sequence is related to Gram-negative D-alanine:D-alanine (D-Ala-D-Ala) ligases [Dutka-Malen, S., Molinas, C., Arthur, M., & Courvalin, P. (1990) Mol. Gen. Genet. 224, 364-372]. We report purification of VanA and demonstrate that it has D-Ala-D-Ala ligase activity but has substantially modified substrate specificity, compared with Gram-negative D-Ala-D-Ala ligases. VanA preferentially condenses D-Ala with D-Met or D-Phe, raising the possibility that its cellular role is to synthesize a modified cell-wall component, which is subsequently not recognized by vancomycin. |
| Links | |
| Keywords |
Amino Acid Sequence; Bacterial Proteins/genetics; Bacterial Proteins/isolation & purification; Bacterial Proteins/metabolism; Carbon-Oxygen Ligases; Chromatography, Gel; Drug Resistance, Microbial/physiology; Gram-Negative Bacteria/enzymology; Molecular Sequence Data; Peptide Synthases/genetics; Peptide Synthases/isolation & purification; Peptide Synthases/metabolism; Streptococcus/drug effects; Streptococcus/enzymology; Substrate Specificity; Vancomycin/pharmacology |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0008716: D-alanine-D-alanine ligase activity |
ECO:0000314: |
F |
"FIGURE 2: Schcmatic figure of the proposed target modification mechanism involving VanA. MurF is a D-Ala-D-Ala adding enzyme; the cross-hatched circle represents an N-acetylmuramyl residue; the open circle represents an N-acetylglucosamine residue. The symbol inside the membrane represents the undecaprenyl lipid carrier. Depicted on the cell surface are the binding of peptidyl-D-Ala-D-Ala by vancomycin and the cross-linking reaction of a modified peptidoglycan terminus." |
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Notes
See also
References
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