Event Title
Defining the Mechanistic Pathway of the Antibiotic Resistance Enzyme OXA-1 Beta Lactamase
Presentation Type
Poster/Portfolio
Presenter Major(s)
Biomedical Sciences
Mentor Information
Rachel Powers
Department
Chemistry
Location
Kirkhof Center KC15
Start Date
11-4-2012 9:00 AM
Keywords
Life Science
Abstract
Beta-lactam antibiotics, such as penicillin, are the biochemical key to preventing bacterial infections. As a result of the expression of four classes (A-D) of beta-lactamase enzymes, bacteria have developed increased resistance to these antibiotics. Class D beta-lactamases are characterized by a serine nucleophile activated by an atypical carboxylated lysine acting as the general base. Little is known about the enzymes' initial recognition of its beta-lactam substrate and the subsequent mechanistic pathway. Of the nearly 160 known Class D beta-lactamases contributing to resistance in bacterial infections like Pseudomonas aeruginosa, OXA -1 represents a subclass exhibiting increased activity against the beta-lactam antibiotic oxacillin. Using a mutant OXA-1 (Ser67Gly), the structure of the enzyme complexed with the hydrolyzed oxacillin product was determined to 1.2 Ã… resolution. This atomic-level structure provides insight into the nuances of Class D beta-lactamase mechanism.
Defining the Mechanistic Pathway of the Antibiotic Resistance Enzyme OXA-1 Beta Lactamase
Kirkhof Center KC15
Beta-lactam antibiotics, such as penicillin, are the biochemical key to preventing bacterial infections. As a result of the expression of four classes (A-D) of beta-lactamase enzymes, bacteria have developed increased resistance to these antibiotics. Class D beta-lactamases are characterized by a serine nucleophile activated by an atypical carboxylated lysine acting as the general base. Little is known about the enzymes' initial recognition of its beta-lactam substrate and the subsequent mechanistic pathway. Of the nearly 160 known Class D beta-lactamases contributing to resistance in bacterial infections like Pseudomonas aeruginosa, OXA -1 represents a subclass exhibiting increased activity against the beta-lactam antibiotic oxacillin. Using a mutant OXA-1 (Ser67Gly), the structure of the enzyme complexed with the hydrolyzed oxacillin product was determined to 1.2 Ã… resolution. This atomic-level structure provides insight into the nuances of Class D beta-lactamase mechanism.