PMID:16038617
| Citation |
Nicola, G, Fedarovich, A, Nicholas, RA and Davies, C (2005) A large displacement of the SXN motif of Cys115-modified penicillin-binding protein 5 from Escherichia coli. Biochem. J. 392:55-63 |
|---|---|
| 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. |
| Links |
PubMed PMC1317664 Online version:10.1042/BJ20050449 |
| Keywords |
Amino Acid Motifs; Binding Sites; Cysteine/genetics; Cysteine/metabolism; Escherichia coli; Models, Molecular; Mutation; Penicillin-Binding Proteins/chemistry; Penicillin-Binding Proteins/genetics; Penicillin-Binding Proteins/metabolism; Protein Conformation |
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