1z6f
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(New page: 200px<br /><applet load="1z6f" size="450" color="white" frame="true" align="right" spinBox="true" caption="1z6f, resolution 1.60Å" /> '''Crystal structure of...)
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Revision as of 05:08, 21 November 2007
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Crystal structure of penicillin-binding protein 5 from E. coli in complex with a boronic acid inhibitor
Overview
Penicillin-binding protein 5 (PBP 5) from Escherichia coli is a, well-characterized d-alanine carboxypeptidase that serves as a, prototypical enzyme to elucidate the structure, function, and catalytic, mechanism of PBPs. A comprehensive understanding of the catalytic, mechanism underlying d-alanine carboxypeptidation and antibiotic binding, has proven elusive. In this study, we report the crystal structure at 1.6, A resolution of PBP 5 in complex with a substrate-like peptide boronic, acid, which was designed to resemble the transition-state intermediate, during the deacylation step of the enzyme-catalyzed reaction with peptide, substrates. In the structure of the complex, the boron atom is covalently, attached to Ser-44, which in turn is within hydrogen-bonding distance to, Lys-47. This arrangement further supports the assignment of Lys-47 as the, general base that activates Ser-44 during acylation. One of the two, hydroxyls in the boronyl center (O2) is held by the oxyanion hole, comprising the amides of Ser-44 and His-216, while the other hydroxyl, (O3), which is analogous to the nucleophilic water for hydrolysis of the, acyl-enzyme intermediate, is solvated by a water molecule that bridges to, Ser-110. Lys-47 is not well-positioned to act as the catalytic base in the, deacylation reaction. Instead, these data suggest a mechanism of catalysis, for deacylation that uses a hydrogen-bonding network, involving Lys-213, Ser-110, and a bridging water molecule, to polarize the hydrolytic water, molecule.
About this Structure
1Z6F is a Single protein structure of sequence from Escherichia coli with BO9 and GOL as ligands. 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 Escherichia coli penicillin-binding protein 5 bound to a tripeptide boronic acid inhibitor: a role for Ser-110 in deacylation., Nicola G, Peddi S, Stefanova M, Nicholas RA, Gutheil WG, Davies C, Biochemistry. 2005 Jun 14;44(23):8207-17. PMID:15938610
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