Crystal structure of the Bacillus subtilis penicillin-binding protein 4a, and its complex with a peptidoglycan mimetic peptide |
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Authors: | Sauvage Eric Duez Colette Herman Raphaël Kerff Frédéric Petrella Stephanie Anderson John W Adediran S A Pratt R F Frère Jean-Marie Charlier Paulette |
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Affiliation: | Centre d'Ingénierie des Protéines, Université de Liège, Institut de Physique B5 et Institut de Chimie B6a, Sart Tilman, B-4000 Liège, Belgium. Eric.Sauvage@ulg.ac.be |
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Abstract: | 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 beta-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. |
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Keywords: | PBP, penicillin-binding protein PBP-A, class A high molecular mass PBP PBP-B, class B high molecular mass PBP PBP-C, class C low molecular mass PBP R39, Actinomadura sp. strain R39 smallcaps" >dd-peptidase R61, Streptomyces R61 smallcaps" >dd-transpeptidase-carboxypeptidase |
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