1KVM : X-ray Crystal Structure of AmpC WT beta-Lactamase in Complex with Covalently Bound Cephalothin

  • Beth M. Beadle (Contributor)
  • Indi Trehan (Contributor)
  • Pamela J Focia (Contributor)
  • Brian K. Shoichet (Contributor)

Dataset

Description

Experimental Technique/Method:X-RAY DIFFRACTION
Resolution:2.06
Classification:HYDROLASE
Release Date:2002-03-13
Deposition Date:2002-01-27
Revision Date:2008-04-27#2011-07-13
Molecular Weight:79609.22
Macromolecule Type:Protein
Residue Count:716
Atom Site Count:5568
DOI:10.2210/pdb1kvm/pdb

Abstract:
Beta-lactamases hydrolyze beta-lactam antibiotics and are the leading cause of bacterial resistance to these drugs. Although beta-lactamases have been extensively studied, structures of the substrate-enzyme and product-enzyme complexes have proven elusive. Here, the structure of a mutant AmpC in complex with the beta-lactam cephalothin in its substrate and product forms was determined by X-ray crystallography to 1.53 A resolution. The acyl-enzyme intermediate between AmpC and cephalothin was determined to 2.06 A resolution. The ligand undergoes a dramatic conformational change as the reaction progresses, with the characteristic six-membered dihydrothiazine ring of cephalothin rotating by 109 degrees. These structures correspond to all three intermediates along the reaction path and provide insight into substrate recognition, catalysis, and product expulsion.
Date made available2002
PublisherRCSB-PDB

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