[en] The genome of Bacillus subtilis encodes 16 penicillin-binding proteins (PBPs) involved in the synthesis and/or remodelling of the peptidoglycan during the complex life cycle of this sporulating Gram-positive rod-shaped bacterium. PBP4a (encoded by the dacC gene) is a low-molecular mass PBP clearly exhibiting in vitro DD-carboxypeptidase activity. We have solved the crystal structure of this protein alone and in complex with a peptide (D-alpha'-aminopymelyl-epsilon-D-alanyl-D-alanine) that mimics the C-terminal end of the Bacillus peptidoglycan stem peptide. PBP4a is composed of three domains: the penicillin-binding domain with a fold similar to the class A 13-lactamase structure and two domains inserted between the conserved motifs 1 and 2 characteristic of the penicillin-recognizing enzymes. The soaking of PBP4a in a solution Of D-alpha-aminopymelyl-epsilon-D-alanyl-D-alanine resulted in an adduct between PBP4a and a D-alpha-aminopimelyl-epsilon-D-alanine dipeptide and an unbound D-alanine, i.e. the products of acylation of PBP4a by D-alpha-aminopymelyl-epsilon-D-alanyl-D-alanine with the release of a D-alanine. The adduct also reveals a binding pocket specific to the diaminopimelic acid, the third residue of the peptidoglycan stem pentapeptide of B. subtilis. This pocket is specific for this class of PBPs. (C) 2007 Elsevier Ltd. All rights reserved.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Sauvage, Eric ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Duez, Colette ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Herman, Raphaël ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Kerff, Frédéric ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Petrella, Stéphanie; Université Pierre et Marie Curie, Paris France > Lab. Recherche Moléculaire sur les Antibiotiques INSERM U655
Anderson, John W.; Wesleyan University, CT USA > Department of Chemistry
Adediran, Suara A.; Wesleyan University, CT USA > Department of Chemistry
Pratt, Rex F.; Wesleyan University, CT USA > Department of Chemistry
Frère, Jean-Marie ; Université de Liège - ULiège > Département des sciences de la vie > Département des sciences de la vie
Charlier, Paulette ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Language :
English
Title :
Crystal structure of the Bacillus subtilis penicillin-binding protein 4a, and its complex with a peptidoglycan mimetic peptide
Publication date :
10 August 2007
Journal title :
Journal of Molecular Biology
ISSN :
0022-2836
eISSN :
1089-8638
Publisher :
Academic Press Ltd Elsevier Science Ltd, London, United Kingdom
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