Disease relevance of Vinylglycine

• This analogue of vinylglycine is a strong inhibitor of the alanine racemases from Pseudomonas aeruginosa and Streptococcus faecalis and of the D-Ala:D-Ala ligase from this latter species [1].

High impact information on Vinylglycine

• The Km for the elimination (deamination) reaction with vinylglycine was 5.6 mM with maximal velocity of 900 min-1 [2].
• The proposed pathway of alkylation of Lys-258 involves abstraction of the alpha proton from vinylglycine, isomerization to the alpha,beta-unsaturated enamine, and subsequent nucleophilic attack of the epsilon-amino group of the lysyl residue at the beta carbon of the inhibitor [3].
• Peptide analyses after inactivation with [1-14C]vinylglycine showed that vinylglycine alkylates the active-site lysine residue 258 which forms the internal aldimine with the coenzyme pyridoxal 5'-phosphate [3].
• Vinylglycine and proparglyglycine show inactivation specificity, then, for L-and D-amino acid oxidase, respectively [4].
• These E-gamma-substituted vinylglycine derivatives were active in displacing [3H]glycine binding from the NMDA receptor-associated recognition site in rat forebrain synaptic plasma membranes, with Ki values in the range of 0.24-8.7 microM [5].

Biological context of Vinylglycine

• Active-site labeling of aspartate aminotransferases by the beta,gamma-unsaturated amino acid vinylglycine [3].

Analytical, diagnostic and therapeutic context of Vinylglycine

• Another promising approach is the stoichiometric titration with specific suicide substrates such as vinylglycine [6].

References