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CRYSTAL STRUCTURE OF A DEACYLATION-DEFECTIVE MUTANT OF PENICILLIN-BINDING PROTEIN 5 MODIFIED BY MERCURYCRYSTAL STRUCTURE OF A DEACYLATION-DEFECTIVE MUTANT OF PENICILLIN-BINDING PROTEIN 5 MODIFIED BY MERCURY
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPenicillin-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. A large displacement of the SXN motif of Cys115-modified penicillin-binding protein 5 from Escherichia coli.,Nicola G, Fedarovich A, Nicholas RA, Davies C Biochem J. 2005 Nov 15;392(Pt 1):55-63. PMID:16038617[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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