1JWZ : Crystal structure of TEM-64 beta-lactamase in complex with a boronic acid inhibitor (105)

  • Xiaojun Wang (Contributor)
  • George Minasov (Contributor)
  • Brian K. Shoichet (Contributor)

Dataset

Description

Experimental Technique/Method:X-RAY DIFFRACTION
Resolution:1.8
Classification:HYDROLASE
Release Date:2002-06-05
Deposition Date:2001-09-05
Revision Date:2008-04-27#2011-07-13
Molecular Weight:29136.35
Macromolecule Type:Protein
Residue Count:263
Atom Site Count:2065
DOI:10.2210/pdb1jwz/pdb

Abstract:
Pressured by antibiotic use, resistance enzymes have been evolving new activities. Does such evolution have a cost? To investigate this question at the molecular level, clinically isolated mutants of the beta-lactamase TEM-1 were studied. When purified, mutant enzymes had increased activity against cephalosporin antibiotics but lost both thermodynamic stability and kinetic activity against their ancestral targets, penicillins. The X-ray crystallographic structures of three mutant enzymes were determined. These structures suggest that activity gain and stability loss is related to an enlarged active site cavity in the mutant enzymes. In several clinically isolated mutant enzymes, a secondary substitution is observed far from the active site (Met182-->Thr). This substitution had little effect on enzyme activity but restored stability lost by substitutions near the active site. This regained stability conferred an advantage in vivo. This pattern of stability loss and restoration may be common in the evolution of new enzyme activity.
Date made available2002
PublisherRCSB-PDB

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