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Literature summary extracted from

  • Van Der Aart, L.; Lemmens, N.; Van Wamel, W.; Van Wezel, G.
    Substrate inhibition of VanA by D-alanine reduces vancomycin resistance in a VanX-dependent manner (2016), Antimicrob. Agents Chemother., 60, 4930-4939 .
    View publication on PubMedView publication on EuropePMC

Inhibitors

EC Number Inhibitors Comment Organism Structure
6.1.2.1 D-alanine substrate inhibition Streptomyces coelicolor

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
6.1.2.1 D-alanine + (R)-lactate + ATP Streptomyces coelicolor
-
 D-alanyl-(R)-lactate + ADP + phosphate
-
 ?
6.1.2.1 D-alanine + (R)-lactate + ATP Streptomyces coelicolor ATCC BAA-471
-
 D-alanyl-(R)-lactate + ADP + phosphate
-
 ?
6.1.2.1 D-alanine + (R)-lactate + ATP Streptomyces coelicolor M145
-
 D-alanyl-(R)-lactate + ADP + phosphate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
3.4.13.22 Streptomyces coelicolor
-
-
-
3.4.13.22 Streptomyces coelicolor ATCC BAA-471
-
-
-
6.1.2.1 Streptomyces coelicolor
-
-
-
6.1.2.1 Streptomyces coelicolor M145
-
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
6.1.2.1 D-alanine + (R)-lactate + ATP
-
 Streptomyces coelicolor D-alanyl-(R)-lactate + ADP + phosphate
-
 ?
6.1.2.1 D-alanine + (R)-lactate + ATP
-
 Streptomyces coelicolor ATCC BAA-471 D-alanyl-(R)-lactate + ADP + phosphate
-
 ?
6.1.2.1 D-alanine + (R)-lactate + ATP
-
 Streptomyces coelicolor M145 D-alanyl-(R)-lactate + ADP + phosphate
-
 ?

Synonyms

EC Number Synonyms Comment Organism
6.1.2.1 D-Ala-D-Lac ligase
-
 Streptomyces coelicolor
6.1.2.1 D-alanyl-D-lactate ligase
-
 Streptomyces coelicolor
6.1.2.1 VanA
-
 Streptomyces coelicolor

Cofactor

EC Number Cofactor Comment Organism Structure
6.1.2.1 ATP
-
 Streptomyces coelicolor

General Information

EC Number General Information Comment Organism
3.4.13.22 physiological function exogenous D-Ala competes with D-Lac as a substrate for ligase VanA and reduces vancomycin resistance. The effect is augmented by several orders of magnitude in the absence of the D-Ala-D-Ala peptidase VanX. High concentrations of D-Ala lead to the production of a significant amount of wild-type cell wall precursors, while vanX-null mutants produce primarily wild-type precursors. This enhances the efficacy of vancomycin in the vancomycin-resistant model organism Streptomyces coelicolor, and the susceptibility of vancomycin-resistant clinical isolates of Enterococcus faecium increases by up to 100fold. The enhanced vancomycin sensitivity of Streptomyces coelicolor cells correlates directly to increased binding of the antibiotic to the cell wall Streptomyces coelicolor