1SDN

CRYSTAL STRUCTURE OF A DEACYLATION-DEFECTIVE MUTANT OF PENICILLIN-BINDING PROTEIN 5 MODIFIED BY MERCURY

Summary for 1SDN

• Entry DOI: 10.2210/pdb1sdn/pdb
• Related: 1NJ4 1NZO 1NZU
• Descriptor: Penicillin-binding protein 5, MERCURY (II) ION (3 entities in total)
• Functional Keywords: peptidoglycan synthesis, penicllin-binding protein, dd-carboxypeptidase, hydrolase
• Biological source: Escherichia coli
• Cellular location: Cell inner membrane; Peripheral membrane protein; Cytoplasmic side: P04287
• Total number of polymer chains: 1
• Total formula weight: 40099.74

Authors

Nicola, G.,Nicholas, R.A.,Davies, C. (deposition date: 2004-02-13, release date: 2005-02-22, Last modification date: 2023-08-23)

Primary citation

Nicola, G.,Fedarovich, A.,Nicholas, R.A.,Davies, C.
A large displacement of the SXN motif of Cys115-modified penicillin-binding protein 5 from Escherichia coli.
Biochem.J., 392:55-63, 2005

PubMed Abstract: Penicillin-binding proteins (PBPs), which are the lethal targets of beta-lactam antibiotics, catalyse the final stages of peptidoglycan biosynthesis of the bacterial cell wall. PBP 5 of Escherichia coli is a D-alanine CPase (carboxypeptidase) that has served as a useful model to elucidate the catalytic mechanism of low-molecular-mass PBPs. Previous studies have shown that modification of Cys115 with a variety of reagents results in a loss of CPase activity and a large decrease in the rate of deacylation of the penicilloyl-PBP 5 complex [Tamura, Imae and Strominger (1976) J. Biol. Chem. 251, 414-423; Curtis and Strominger (1978) J. Biol. Chem. 253, 2584-2588]. The crystal structure of wild-type PBP 5 in which Cys115 fortuitously had formed a covalent adduct with 2-mercaptoethanol was solved at 2.0 A (0.2 nm) resolution, and these results provide a structural rationale for how thiol-directed reagents lower the rate of deacylation. When compared with the structure of the unmodified wild-type enzyme, a major change in the architecture of the active site is observed. The two largest differences are the disordering of a loop comprising residues 74-90 and a shift in residues 106-111, which results in the displacement of Ser110 of the SXN active-site motif. These results support the developing hypothesis that the SXN motif of PBP 5, and especially Ser110, is intimately involved in the catalytic mechanism of deacylation.

PubMed: 16038617
DOI: 10.1042/BJ20050449

Experimental method

X-RAY DIFFRACTION (2.5 Å)