4K91

Crystal structure of Penicillin-Binding Protein 5 (PBP5) from Pseudomonas aeruginosa in apo state

Summary for 4K91

• Entry DOI: 10.2210/pdb4k91/pdb
• Descriptor: D-ala-D-ala-carboxypeptidase, SUCCINIC ACID (3 entities in total)
• Functional Keywords: dd-carboxypeptidase, membrane associated, hydrolase
• Biological source: Pseudomonas aeruginosa UCBPP-PA14
• Total number of polymer chains: 2
• Total formula weight: 75984.13

Authors

Smith, J.,Toth, M.,Vakulenko, S.,Mobashery, S.,Chen, Y. (deposition date: 2013-04-19, release date: 2013-09-25, Last modification date: 2024-02-28)

Primary citation

Smith, J.D.,Kumarasiri, M.,Zhang, W.,Hesek, D.,Lee, M.,Toth, M.,Vakulenko, S.,Fisher, J.F.,Mobashery, S.,Chen, Y.
Structural analysis of the role of Pseudomonas aeruginosa penicillin-binding protein 5 in beta-lactam resistance.
Antimicrob.Agents Chemother., 57:3137-3146, 2013

PubMed Abstract: Penicillin-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 β-lactamase activity to contribute to the ability of P. aeruginosa to resist the antibiotic activity of the β-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 β-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 β-lactamase activities. Its crystal structure at a 2.05-Å resolution shows features closely resembling those of the class A β-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 β-lactam resistance of P. aeruginosa while highlighting how broader β-lactamase activity may be encoded in the structural folds shared by the PBP and serine β-lactamase classes.

PubMed: 23629710
DOI: 10.1128/AAC.00505-13

Experimental method

X-RAY DIFFRACTION (2.05 Å)