1z6f
From Proteopedia
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'''Crystal structure of penicillin-binding protein 5 from E. coli in complex with a boronic acid inhibitor''' | '''Crystal structure of penicillin-binding protein 5 from E. coli in complex with a boronic acid inhibitor''' | ||
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[[Category: Peddi, S.]] | [[Category: Peddi, S.]] | ||
[[Category: Stefanova, M.]] | [[Category: Stefanova, M.]] | ||
| - | [[Category: | + | [[Category: Boronic acid]] |
| - | [[Category: | + | [[Category: Dd-carboxypeptidase]] |
| - | [[Category: | + | [[Category: Hydrolase]] |
| - | [[Category: | + | [[Category: Penicillin-binding protein]] |
| - | [[Category: | + | [[Category: Peptidoglycan synthesis]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 17:13:56 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 14:13, 3 May 2008
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 Sat May 3 17:13:56 2008
