1HD8

Crystal structure of a deacylation-defective mutant of penicillin-binding protein 5 at 2.3 A resolution

Summary for 1HD8

• Entry DOI: 10.2210/pdb1hd8/pdb
• Descriptor: PENICILLIN-BINDING PROTEIN 5 (2 entities in total)
• Functional Keywords: peptidoglycan synthesis, penicillin-binding protein, dd-carboxypeptidase, hydrolase
• Biological source: ESCHERICHIA COLI
• Total number of polymer chains: 1
• Total formula weight: 39899.15

Authors

Davies, C.,White, S.W.,Nicholas, R.A. (deposition date: 2000-11-11, release date: 2001-11-08, Last modification date: 2024-05-08)

Primary citation

Davies, C.,White, S.W.,Nicholas, R.A.
Crystal Structure of a Deacylation-Defective Mutant of Penicillin-Binding Protein 5 at 2.3-A Resolution
J.Biol.Chem., 276:616-, 2001

PubMed Abstract: Penicillin-binding protein 5 (PBP 5) of Escherichia coli functions as a d-alanine carboxypeptidase, cleaving the C-terminal d-alanine residue from cell wall peptides. Like all PBPs, PBP 5 forms a covalent acyl-enzyme complex with beta-lactam antibiotics; however, PBP 5 is distinguished by its high rate of deacylation of the acyl-enzyme complex (t(12) approximately 9 min). A Gly-105 --> Asp mutation in PBP 5 markedly impairs this beta-lactamase activity (deacylation), with only minor effects on acylation, and promotes accumulation of a covalent complex with peptide substrates. To gain further insight into the catalytic mechanism of PBP 5, we determined the three-dimensional structure of the G105D mutant form of soluble PBP 5 (termed sPBP 5') at 2.3 A resolution. The structure is composed of two domains, a penicillin binding domain with a striking similarity to Class A beta-lactamases (TEM-1-like) and a domain of unknown function. In addition, the penicillin-binding domain contains an active site loop spatially equivalent to the Omega loop of beta-lactamases. In beta-lactamases, the Omega loop contains two amino acids involved in catalyzing deacylation. This similarity may explain the high beta-lactamase activity of wild-type PBP 5. Because of the low rate of deacylation of the G105D mutant, visualization of peptide substrates bound to the active site may be possible.

PubMed: 10967102
DOI: 10.1074/JBC.M004471200

Experimental method

X-RAY DIFFRACTION (2.3 Å)