Reference : Substrate Specificity of Low-Molecular Mass Bacterial DD-Peptidases
Scientific journals : Article
Life sciences : Microbiology
Substrate Specificity of Low-Molecular Mass Bacterial DD-Peptidases
[fr] Spécificité de substrat des DD-peptidases bactériennes de faible poids moléculaire
Nemmara, Venkatesh V [Wesleyan university, connecticut 06459 USA > Department of Chemistry > > >]
Dzhekieva, Liudmila [Wesleyan university, connecticut 06459 USA > Department of Chemistry > > >]
Subarno Sakar, Kumar [Wesleyan University, Connecticut 06459, USA > Department of Chemistry > > >]
Adediran, S. A. [Wesleyan University, Connecticut 06459, USA > Department of Chemistry > > >]
Duez, Colette mailto [Université de Liège - ULiège > > Centre d'ingénierie des protéines >]
Nicholas, Robert A. [University of North Carolina, North Carolina 27599-7365, USA > Department of Pharmacology > > >]
Pratt, Rex F. mailto [Wesleyan University, Connecticut 06459, USA > Department of Chemistry > > >]
American Chemical Society
Yes (verified by ORBi)
[en] DD-peptidases ; Enzymology
[en] The bacterial DD-peptidases or penicillin-binding proteins (PBPs) catalyze the formation and regulation of cross-links in peptidoglycan biosynthesis. They are classified into two groups, the high-molecular mass (HMM) and lowmolecular mass (LMM) enzymes. The latter group, which is subdivided into classes A−C (LMMA, -B, and -C, respectively), is believed to catalyze DD-carboxypeptidase and endopeptidase reactions in vivo. To date, the specificity of their reactions with particular elements of peptidoglycan structure has not, in general, been defined.
This paper describes the steady-state kinetics of hydrolysis of a series of specific
peptidoglycan-mimetic peptides, representing various elements of stem peptide structure, catalyzed by a range of LMM PBPs (the LMMA enzymes, Escherichia coli PBP5, Neisseria gonorrhoeae PBP4, and Streptococcus pneumoniae PBP3, and the LMMC enzymes, the Actinomadura R39 DD-peptidase, Bacillus subtilis PBP4a, and N. gonorrhoeae PBP3). The R39 enzyme (LMMC), like the previously studied Streptomyces R61 DD-peptidase (LMMB), specifically and rapidly hydrolyzes stem peptide fragments with a free N-terminus. In accord with this result, the crystal structures of the R61 and R39 enzymes display a binding site specific to the stem peptide N-terminus. These are water-soluble enzymes, however, with no known specific function in vivo. On the other hand, soluble versions of the remaining enzymes of those noted above, all of which are likely to be membrane-bound and/or associated in vivo and have been assigned particular roles in cell wall biosynthesis and maintenance, show little or no specificity for peptides containing elements of peptidoglycan structure. Peptidoglycan-mimetic boronate transition-state analogues do inhibit these enzymes but display notable specificity only for the LMMC enzymes, where, unlike peptide substrates, they may be
able to effectively induce a specific active site structure. The manner in which LMMA (and HMM) DD-peptidases achieve substrate specificity, both in vitro and in vivo, remains unknown.
Department of £chemistry, Wesleyan university
NIH grant AI-17986 and AI-36901- FNRS and Belgian PAI 6/19
Researchers ; Professionals ; Students

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