| http://purl.uniprot.org/citations/27622530 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27622530 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27622530 | http://www.w3.org/2000/01/rdf-schema#comment | "Emerging β-lactamase-mediated resistance is threatening the clinical utility of the single most prominent class of antibacterial agents used in medicine, the β-lactams. The diazabicyclooctane avibactam is able to inhibit a wider range of serine β-lactamases than has been previously observed with β-lactamase inhibitors such as the widely prescribed clavulanic acid. However, despite its broad-spectrum activity, variable levels of inhibition have been observed for molecular class D β-lactamases. In order to better understand the molecular basis and spectrum of inhibition by avibactam, we provide structural and mechanistic analysis of the compound in complex with important class A and D serine β-lactamases. Herein, we reveal the 1.7- and 2.0-Å-resolution crystal structures of avibactam covalently bound to class D β-lactamases OXA-10 and OXA-48. Furthermore, a kinetic analysis of key active-site mutants for class A β-lactamase CTX-M-15 allows us to propose a validated mechanism for avibactam-mediated β-lactamase inhibition including a unique role for S130, which acts as a general base. This study provides molecular insights that will aid in the design and development of avibactam-based chemotherapeutic agents effective against emerging drug-resistant microorganisms."xsd:string |
| http://purl.uniprot.org/citations/27622530 | http://purl.org/dc/terms/identifier | "doi:10.1021/acsinfecdis.5b00007"xsd:string |
| http://purl.uniprot.org/citations/27622530 | http://purl.org/dc/terms/identifier | "doi:10.1021/acsinfecdis.5b00007"xsd:string |
| http://purl.uniprot.org/citations/27622530 | http://purl.uniprot.org/core/author | "Wright G.D."xsd:string |
| http://purl.uniprot.org/citations/27622530 | http://purl.uniprot.org/core/author | "Wright G.D."xsd:string |
| http://purl.uniprot.org/citations/27622530 | http://purl.uniprot.org/core/author | "Strynadka N.C."xsd:string |
| http://purl.uniprot.org/citations/27622530 | http://purl.uniprot.org/core/author | "Strynadka N.C."xsd:string |
| http://purl.uniprot.org/citations/27622530 | http://purl.uniprot.org/core/author | "King D.T."xsd:string |
| http://purl.uniprot.org/citations/27622530 | http://purl.uniprot.org/core/author | "King D.T."xsd:string |
| http://purl.uniprot.org/citations/27622530 | http://purl.uniprot.org/core/author | "King A.M."xsd:string |
| http://purl.uniprot.org/citations/27622530 | http://purl.uniprot.org/core/author | "King A.M."xsd:string |
| http://purl.uniprot.org/citations/27622530 | http://purl.uniprot.org/core/author | "Lal S.M."xsd:string |
| http://purl.uniprot.org/citations/27622530 | http://purl.uniprot.org/core/author | "Lal S.M."xsd:string |
| http://purl.uniprot.org/citations/27622530 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/27622530 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/27622530 | http://purl.uniprot.org/core/name | "ACS Infect. Dis."xsd:string |
| http://purl.uniprot.org/citations/27622530 | http://purl.uniprot.org/core/name | "ACS Infect Dis"xsd:string |
| http://purl.uniprot.org/citations/27622530 | http://purl.uniprot.org/core/pages | "175-184"xsd:string |
| http://purl.uniprot.org/citations/27622530 | http://purl.uniprot.org/core/pages | "175-184"xsd:string |
| http://purl.uniprot.org/citations/27622530 | http://purl.uniprot.org/core/title | "Molecular Mechanism of Avibactam-Mediated beta-Lactamase Inhibition."xsd:string |
| http://purl.uniprot.org/citations/27622530 | http://purl.uniprot.org/core/title | "Molecular Mechanism of Avibactam-Mediated beta-Lactamase Inhibition."xsd:string |
| http://purl.uniprot.org/citations/27622530 | http://purl.uniprot.org/core/volume | "1"xsd:string |
| http://purl.uniprot.org/citations/27622530 | http://purl.uniprot.org/core/volume | "1"xsd:string |