Amini, Kaveh2020-07-142020-07-142012-042012-04-25978-0-494-90084-0http://hdl.handle.net/10315/37636OXA-58 enzyme from Acinetobacter baumannii is a carbepenm-hydrolyzing class-D β-lactamase which uses a carbamylated lysine to activate the nucleophilic serine used for β-lactam hydrolysis. The deacylating water molecule approaches the acylenzyme intermediate formed between the enzyme and the β-lactam from the α-face. According to our findings, OXA-58 uses the same catalytic machinery observed in class D β-lactamases such as OXA-10. Comparison of active site shape in OXA-58, OXA-24 and OXA-48 with the OXA-10 β-lactamase suggests that these carbapenem-hydrolyzing class D β-lactamases have gained the capability of hydrolyzing imipenem, an important carbapenem in clinical use, by slight structural changes in the active site. Also, investigation of the kinetics of β-lactam hydrolysis by Phen113A, Phen114A, Met225A, Phen113Tyr, Phen114l1e and Met225Thr shows that penicillin G is hydrolyzed better than amoxicillin and ampicillin which are hydrolyzed with comparable catalytic efficiencies. Carbenicillin was the poorest substrate.enAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.BiochemistryOrganic ChemistryElectronic Thesis or Dissertation