On the substrate specificity of bacterial DD-peptidases: evidence from two series of peptidoglycan-mimetic peptides.
The reactions between bacterial DD-peptidases and beta-lactam antibiotics have been studied for many years. Less well understood are the interactions between these enzymes and their natural substrates, presumably the peptide moieties of peptidoglycan. In general, remarkably little activity has previously been demonstrated in vitro against potential peptide substrates, although in many cases the peptides employed were non-specific and not homologous with the relevant peptidoglycan. In this paper, the specificity of a panel of DD-peptidases against elements of species-specific D-alanyl-D-alanine peptides has been assessed. In two cases, those of soluble, low-molecular-mass DD-peptidases, high activity against the relevant peptides has been demonstrated. In these cases, the high specificity is towards the free N-terminus of the peptidoglycan fragment. With a number of other enzymes, particularly high-molecular-mass DD-peptidases, little or no activity against these peptides was observed. In separate experiments, the reactivity of the enzymes against the central, largely invariant, peptide stem was examined. None of the enzymes surveyed showed high activity against this structural element although weak specificity in the expected direction towards the one structural variable (D-gammaGln versus D-gammaGlu) was observed. The current state of understanding of the activity of these enzymes in vitro is discussed.
Anderson
John W
JW
Department of Chemistry, Wesleyan University, Middletown, CT 06459, USA.
Adediran
Suara A
SA
Charlier
Paulette
P
Nguyen-Distèche
Martine
M
Frère
Jean-Marie
JM
Nicholas
Robert A
RA
Pratt
Rex F
RF
D001419:Bacteria / Q000201:enzymology*; D002268:Carboxypeptidases / Q000378:metabolism*; D007700:Kinetics; D018716:Molecular Mimicry; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase; D013379:Substrate Specificity
D002268:Carboxypeptidases; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase