1nzo

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spinqualitylabelsall models 1nzo, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

The crystal structure of wild type penicillin-binding protein 5 from E. coli

Overview

Penicillin-binding protein 5 (PBP 5) of Escherichia coli functions as a, d-alanine carboxypeptidase (CPase), cleaving d-alanine from the C terminus, of 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 acylenzyme complex (t(1/2), approximately 10 min). A Gly105 --> Asp mutation in PBP 5 markedly impairs, deacylation with only minor effects on acylation, and abolishes CPase, activity. We have determined the three-dimensional structure of a soluble, form of wild-type PBP 5 at 1.85-A resolution and have also refined the, structure of the G105D mutant form of PBP 5 to 1.9-A resolution., Comparison of the two structures reveals that the major effect of the, mutation is to disorder a loop comprising residues 74-90 that sits atop, the SXN motif of the active site. Deletion of the 74-90 loop in wild-type, PBP 5 markedly diminished the deacylation rate of penicillin G with a, minimal impact on acylation, and abolished CPase activity. These effects, were very similar to those observed in the G105D mutant, reinforcing the, idea that this mutation causes disordering of the 74-90 loop. Mutation of, two consecutive serines within this loop, which hydrogen bond to Ser110, and Asn112 in the SXN motif, had marked effects on CPase activity, but not, beta-lactam antibiotic binding or hydrolysis. These data suggest a direct, role for the SXN motif in deacylation of the acyl-enzyme complex and imply, that the functioning of this motif is modulated by the 74-90 loop.

About this Structure

1NZO is a Single protein structure of sequence from Escherichia coli with BME as ligand. Active as Serine-type D-Ala-D-Ala carboxypeptidase, with EC number 3.4.16.4 Full crystallographic information is available from OCA.

Reference

Crystal structure of wild-type penicillin-binding protein 5 from Escherichia coli: implications for deacylation of the acyl-enzyme complex., Nicholas RA, Krings S, Tomberg J, Nicola G, Davies C, J Biol Chem. 2003 Dec 26;278(52):52826-33. Epub 2003 Oct 10. PMID:14555648

Page seeded by OCA on Tue Nov 20 22:41:27 2007