title: Breakdown of the stereospecificity of DD-peptidases and beta-lactamases with thiolester substrates.
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 beta-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 beta-lactamase also hydrolysed thiolesters containing an L residue in the penultimate position, sometimes with a higher efficiency than the D isomer.
authors.affiliation: Laboratoire d'Enzymologie, Université de Liège, Institut de Chimie, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Damblon
authors.forename: G H
authors.initials: GH
authors.lastname: Zhao
authors.forename: M
authors.initials: M
authors.lastname: Jamin
authors.forename: P
authors.initials: P
authors.lastname: Ledent
authors.forename: A
authors.initials: A
authors.lastname: Dubus
authors.forename: M
authors.initials: M
authors.lastname: Vanhove
authors.forename: X
authors.initials: X
authors.lastname: Raquet
authors.forename: L
authors.initials: L
authors.lastname: Christiaens
authors.forename: J M
authors.initials: JM
authors.lastname: Frère
mesh_terms: D000595:Amino Acid Sequence; D004952:Esters; D007700:Kinetics; D008969:Molecular Sequence Data; D002267:Muramoylpentapeptide Carboxypeptidase / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity; D013438:Sulfhydryl Compounds; D001618:beta-Lactamases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004952:Esters; D013438:Sulfhydryl Compounds; D002267:Muramoylpentapeptide Carboxypeptidase; D001618:beta-Lactamases