1z6f
From Proteopedia
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| , resolution 1.60Å | |||||||
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| Ligands: | , | ||||||
| Gene: | dacA, pfv (Escherichia coli) | ||||||
| Activity: | Serine-type D-Ala-D-Ala carboxypeptidase, with EC number 3.4.16.4 | ||||||
| Related: | 1NZO, 1NJ4, 1NZU, 1SDN
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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
Page seeded by OCA on Mon Mar 31 01:29:47 2008
