A Close Look at the Hydrolytic Mechanism of OXA-58, a Class D β-Lactamase from Acinetobacter baumannii
| dc.contributor.author | Amini, Kaveh | |
| dc.date.accessioned | 2020-07-14T19:44:32Z | |
| dc.date.available | 2020-07-14T19:44:32Z | |
| dc.date.copyright | 2012-04 | |
| dc.date.issued | 2012-04-25 | |
| dc.degree.discipline | Chemistry | |
| dc.degree.level | Master's | |
| dc.degree.name | Master of Science | |
| dc.description.abstract | OXA-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. | en_US |
| dc.identifier.isbn | 978-0-494-90084-0 | |
| dc.identifier.uri | http://hdl.handle.net/10315/37636 | |
| dc.language.iso | en | en_US |
| dc.rights | Author owns copyright, except where explicitly noted. Please contact the author directly with licensing requests. | en_US |
| dc.subject | Biochemistry | en_US |
| dc.subject | Organic Chemistry | en_US |
| dc.title | A Close Look at the Hydrolytic Mechanism of OXA-58, a Class D β-Lactamase from Acinetobacter baumannii | en_US |
| dc.type | Electronic Thesis or Dissertation | en_US |