Event Title
Effects of Asn152 Mutation on Substrate Selectivity of P99 Cephalosporinase
Presentation Type
Poster/Portfolio
Presenter Major(s)
Cell and Molecular Biology, Biology
Mentor Information
Rachel Powers, powersra@gvsu.edu
Department
Chemistry
Location
Henry Hall Atrium 101
Start Date
13-4-2011 10:00 AM
End Date
13-4-2011 11:00 AM
Keywords
Life Science
Abstract
Beta-lactams are a widely administered group of antibiotics that disrupt cell wall synthesis by inactivating bacterial transpeptidase enzymes. Unfortunately, an increasing number of bacteria resistant to beta-lactams have emerged that utilize beta-lactamases. These enzymes render the antibiotic inactive. Of particular concern is the appearance of extended-spectrum beta-lactamases. The class C beta-lactamase P99 is known as a cephalosporinase. Mutation of the highly conserved N152 residue has a substantial effect on substrate selectivity. Three of these mutants, N152S, N152G, and N152T exhibit a substrate selectivity switch, and the structural basis for this is not understood. Each mutant was successfully purified, and two of the mutants have been crystallized. Initial crystallization conditions are being optimized for improved diffraction. The X-ray crystal structure of an extended spectrum beta-lactamase may provide insight into how resistance develops.
Effects of Asn152 Mutation on Substrate Selectivity of P99 Cephalosporinase
Henry Hall Atrium 101
Beta-lactams are a widely administered group of antibiotics that disrupt cell wall synthesis by inactivating bacterial transpeptidase enzymes. Unfortunately, an increasing number of bacteria resistant to beta-lactams have emerged that utilize beta-lactamases. These enzymes render the antibiotic inactive. Of particular concern is the appearance of extended-spectrum beta-lactamases. The class C beta-lactamase P99 is known as a cephalosporinase. Mutation of the highly conserved N152 residue has a substantial effect on substrate selectivity. Three of these mutants, N152S, N152G, and N152T exhibit a substrate selectivity switch, and the structural basis for this is not understood. Each mutant was successfully purified, and two of the mutants have been crystallized. Initial crystallization conditions are being optimized for improved diffraction. The X-ray crystal structure of an extended spectrum beta-lactamase may provide insight into how resistance develops.