Sauvage Eric, Duez Colette, Herman Raphaël, Kerff Frédéric, Petrella Stephanie, Anderson John W, Adediran S A, Pratt R F, Frère Jean-Marie, Charlier Paulette
Centre d'Ingénierie des Protéines, Université de Liège, Institut de Physique B5 et Institut de Chimie B6a, Sart Tilman, B-4000 Liège, Belgium.
J Mol Biol. 2007 Aug 10;371(2):528-39. doi: 10.1016/j.jmb.2007.05.071. Epub 2007 Jun 2.
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.
枯草芽孢杆菌的基因组编码16种青霉素结合蛋白(PBPs),这些蛋白在这种形成芽孢的革兰氏阳性杆状细菌的复杂生命周期中参与肽聚糖的合成和/或重塑。PBP4a(由dacC基因编码)是一种低分子量的PBP,在体外明显表现出DD-羧肽酶活性。我们已经解析了该蛋白单独以及与一种模拟枯草芽孢杆菌肽聚糖茎肽C末端的肽(D-α-氨基庚二酸-ε-D-丙氨酰-D-丙氨酸)形成复合物时的晶体结构。PBP4a由三个结构域组成:青霉素结合结构域,其折叠方式类似于A类β-内酰胺酶结构;以及插入在青霉素识别酶特有的保守基序1和2之间的两个结构域。将PBP4a浸泡在D-α-氨基庚二酸-ε-D-丙氨酰-D-丙氨酸溶液中,会导致PBP4a与一个D-α-氨基庚二酸-ε-D-丙氨酰-D-丙氨酸二肽以及一个未结合的D-丙氨酸形成加合物,即D-α-氨基庚二酸-ε-D-丙氨酰-D-丙氨酸对PBP4a进行酰化反应并释放出一个D-丙氨酸后的产物。该加合物还揭示了一个对二氨基庚二酸特异的结合口袋,二氨基庚二酸是枯草芽孢杆菌肽聚糖茎五肽的第三个残基。这个口袋对这类PBPs具有特异性。