Accueil > Publications > Recherche par années > Années 1990 > 1995

Damblon, C ; Zhao, GH ; Jamin, M ; Ledent, P ; Dubus, A ; Vanhove, M ; Raquet, X ; Christiaens, L ; Frère, JM

Breakdown of the stereospecificity of DD-peptidases and ß-lactamases with thioester substrates

Biochemical Journal 309 431-436

par Administrateur - publié le

Abstract :

With peptide analogues of their natural substrates (the glycopeptide units of nascent peptidoglycan), the DD-peptidases exhibit a strict preference for D-Ala-D-Xaa C-termini. Gly is tolerated as the C-terminal residue, but with a significantly decreased activity. These enzymes were also known to hydrolyse various ester and thiolester analogues of their natural substrates. Some thiolesters with a C-terminal leaving group that exhibited L stereochemistry were significantly hydrolysed by some of the enzymes, particularly the Actinomadura R39 DD-peptidase, but the strict specificity for a D residue in the penultimate position was fully retained. These esters and thiolesters also behave as substrates for ß-lactamases. In this case, thiolesters exhibiting L stereochemistry in the ultimate position could also be hydrolysed, mainly by the class-C and class-D enzymes. However, more surprisingly, the class-C Enterobacter cloacae P99 ß-lactamase also hydrolysed thiolesters containing an L residue in the penultimate position, sometimes with a higher efficiency than the D isomer.