PMID:19807181
| Citation |
Chen, Y, Zhang, W, Shi, Q, Hesek, D, Lee, M, Mobashery, S and Shoichet, BK (2009) Crystal structures of penicillin-binding protein 6 from Escherichia coli. J. Am. Chem. Soc. 131:14345-54 |
|---|---|
| Abstract |
Penicillin-binding protein 6 (PBP6) is one of the two main DD-carboxypeptidases in Escherichia coli, which are implicated in maturation of bacterial cell wall and formation of cell shape. Here, we report the first X-ray crystal structures of PBP6, capturing its apo state (2.1 A), an acyl-enzyme intermediate with the antibiotic ampicillin (1.8 A), and for the first time for a PBP, a preacylation complex (a "Michaelis complex", determined at 1.8 A) with a peptidoglycan substrate fragment containing the full pentapeptide, NAM-(L-Ala-D-isoGlu-L-Lys-D-Ala-D-Ala). These structures illuminate the molecular interactions essential for ligand recognition and catalysis by DD-carboxypeptidases, and suggest a coupling of conformational flexibility of active site loops to the reaction coordinate. The substrate fragment complex structure, in particular, provides templates for models of cell wall recognition by PBPs, as well as substantiating evidence for the molecular mimicry by beta-lactam antibiotics of the peptidoglycan acyl-D-Ala-D-Ala moiety. |
| Links |
PubMed Online version:10.1021/ja903773f |
| Keywords |
Ampicillin/chemistry; Catalytic Domain; Crystallography, X-Ray; Dipeptidases/biosynthesis; Dipeptidases/chemistry; Dipeptidases/genetics; Escherichia coli/enzymology; Escherichia coli/genetics; Escherichia coli Proteins/biosynthesis; Escherichia coli Proteins/chemistry; Escherichia coli Proteins/genetics; Models, Molecular; Penicillin-Binding Proteins/biosynthesis; Penicillin-Binding Proteins/chemistry; Penicillin-Binding Proteins/genetics; Peptide Fragments/chemistry; Structure-Activity Relationship |
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