1jwp
Structure of M182T mutant of TEM-1 beta-lactamase
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OverviewOverview
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.
About this StructureAbout this Structure
1JWP is a Single protein structure of sequence from Escherichia coli with PO4 as ligand. Active as Beta-lactamase, with EC number 3.5.2.6 Full crystallographic information is available from OCA.
ReferenceReference
Evolution of an antibiotic resistance enzyme constrained by stability and activity trade-offs., Wang X, Minasov G, Shoichet BK, J Mol Biol. 2002 Jun 28;320(1):85-95. PMID:12079336
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