4k91
From Proteopedia
Crystal structure of Penicillin-Binding Protein 5 (PBP5) from Pseudomonas aeruginosa in apo state
Structural highlights
FunctionA0A0H2ZFH3_PSEAB Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors.[ARBA:ARBA00003217] Publication Abstract from PubMedPenicillin-binding protein 5 (PBP5) is one of the most abundant PBPs in Pseudomonas aeruginosa. Although its main function is that of a cell wall dd-carboxypeptidase, it possesses sufficient beta-lactamase activity to contribute to the ability of P. aeruginosa to resist the antibiotic activity of the beta-lactams. The study of these dual activities is important for understanding the mechanisms of antibiotic resistance by P. aeruginosa, an important human pathogen, and to the understanding of the evolution of beta-lactamase activity from the PBP enzymes. We purified a soluble version of P. aeruginosa PBP5 (designated Pa sPBP5) by deletion of its C-terminal membrane anchor. Under in vitro conditions, Pa sPBP5 demonstrates both dd-carboxypeptidase and expanded-spectrum beta-lactamase activities. Its crystal structure at a 2.05-A resolution shows features closely resembling those of the class A beta-lactamases, including a shortened loop spanning residues 74 to 78 near the active site and with respect to the conformations adopted by two active-site residues, Ser101 and Lys203. These features are absent in the related PBP5 of Escherichia coli. A comparison of the two Pa sPBP5 monomers in the asymmetric unit, together with molecular dynamics simulations, revealed an active-site flexibility that may explain its carbapenemase activity, a function that is absent in the E. coli PBP5 enzyme. Our functional and structural characterizations underscore the versatility of this PBP5 in contributing to the beta-lactam resistance of P. aeruginosa while highlighting how broader beta-lactamase activity may be encoded in the structural folds shared by the PBP and serine beta-lactamase classes. Structural analysis of the role of Pseudomonas aeruginosa penicillin-binding protein 5 in beta-lactam resistance.,Smith JD, Kumarasiri M, Zhang W, Hesek D, Lee M, Toth M, Vakulenko S, Fisher JF, Mobashery S, Chen Y Antimicrob Agents Chemother. 2013 Jul;57(7):3137-46. doi: 10.1128/AAC.00505-13., Epub 2013 Apr 29. PMID:23629710[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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