| http://purl.uniprot.org/citations/22296601 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22296601 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22296601 | http://www.w3.org/2000/01/rdf-schema#comment | "The emergence of CTX-M class A extended-spectrum β-lactamases poses a serious health threat to the public. We have applied structure-based design to improve the potency of a novel noncovalent tetrazole-containing CTX-M inhibitor (K(i) = 21 μM) more than 200-fold via structural modifications targeting two binding hot spots, a hydrophobic shelf formed by Pro167 and a polar site anchored by Asp240. Functional groups contacting each binding hot spot independently in initial designs were later combined to produce analogues with submicromolar potencies, including 6-trifluoromethyl-3H-benzoimidazole-4-carboxylic acid [3-(1H-tetrazol-5-yl)-phenyl]-amide, which had a K(i) value of 89 nM and reduced the MIC of cefotaxime by 64-fold in CTX-M-9 expressing Escherichia coli . The in vitro potency gains were accompanied by improvements in ligand efficiency (from 0.30 to 0.39) and LipE (from 1.37 to 3.86). These new analogues represent the first nM-affinity noncovalent inhibitors of a class A β-lactamase. Their complex crystal structures provide valuable information about ligand binding for future inhibitor design."xsd:string |
| http://purl.uniprot.org/citations/22296601 | http://purl.org/dc/terms/identifier | "doi:10.1021/jm2014138"xsd:string |
| http://purl.uniprot.org/citations/22296601 | http://purl.org/dc/terms/identifier | "doi:10.1021/jm2014138"xsd:string |
| http://purl.uniprot.org/citations/22296601 | http://purl.uniprot.org/core/author | "Chen Y."xsd:string |
| http://purl.uniprot.org/citations/22296601 | http://purl.uniprot.org/core/author | "Chen Y."xsd:string |
| http://purl.uniprot.org/citations/22296601 | http://purl.uniprot.org/core/author | "Liu G."xsd:string |
| http://purl.uniprot.org/citations/22296601 | http://purl.uniprot.org/core/author | "Liu G."xsd:string |
| http://purl.uniprot.org/citations/22296601 | http://purl.uniprot.org/core/author | "Smith E."xsd:string |
| http://purl.uniprot.org/citations/22296601 | http://purl.uniprot.org/core/author | "Smith E."xsd:string |
| http://purl.uniprot.org/citations/22296601 | http://purl.uniprot.org/core/author | "Jaishankar P."xsd:string |
| http://purl.uniprot.org/citations/22296601 | http://purl.uniprot.org/core/author | "Jaishankar P."xsd:string |
| http://purl.uniprot.org/citations/22296601 | http://purl.uniprot.org/core/author | "Renslo A.R."xsd:string |
| http://purl.uniprot.org/citations/22296601 | http://purl.uniprot.org/core/author | "Renslo A.R."xsd:string |
| http://purl.uniprot.org/citations/22296601 | http://purl.uniprot.org/core/author | "Bonnet R."xsd:string |
| http://purl.uniprot.org/citations/22296601 | http://purl.uniprot.org/core/author | "Bonnet R."xsd:string |
| http://purl.uniprot.org/citations/22296601 | http://purl.uniprot.org/core/author | "Beyrouthy R."xsd:string |
| http://purl.uniprot.org/citations/22296601 | http://purl.uniprot.org/core/author | "Beyrouthy R."xsd:string |
| http://purl.uniprot.org/citations/22296601 | http://purl.uniprot.org/core/author | "Nichols D.A."xsd:string |
| http://purl.uniprot.org/citations/22296601 | http://purl.uniprot.org/core/author | "Nichols D.A."xsd:string |
| http://purl.uniprot.org/citations/22296601 | http://purl.uniprot.org/core/author | "Larson W."xsd:string |
| http://purl.uniprot.org/citations/22296601 | http://purl.uniprot.org/core/author | "Larson W."xsd:string |
| http://purl.uniprot.org/citations/22296601 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22296601 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |