| http://purl.uniprot.org/citations/30150473 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30150473 | http://www.w3.org/2000/01/rdf-schema#comment | "β-Lactam antibiotics are the mainstay for the treatment of bacterial infections. However, elevated resistance to these antibiotics mediated by metallo-β-lactamases (MBLs) has become a global concern. New Delhi metallo-β-lactamase-1 (NDM-1), a newly added member of the MBL family that can hydrolyze almost all β-lactam antibiotics, has rapidly spread all over the world and poses serious clinical threats. Broad-spectrum and mechanism-based inhibitors against all MBLs are highly desired, but the differential mechanisms of MBLs toward different antibiotics pose a great challenge. To facilitate the design of mechanism-based inhibitors, we investigated the active-site conformational changes of NDM-1 through the determination of a series of 15 high-resolution crystal structures in native form and in complex with products and by using biochemical and biophysical studies, site-directed mutagenesis, and molecular dynamics computation. The structural studies reveal the consistency of the active-site conformations in NDM-1/product complexes and the fluctuation in native NDM-1 structures. The enzymatic measurements indicate a correlation between enzymatic activity and the active-site fluctuation, with more fluctuation favoring higher activity. This correlation is further validated by structural and enzymatic studies of the Q123G mutant. Our combinational studies suggest that active-site conformational fluctuation promotes the enzymatic activity of NDM-1, which may guide further mechanism studies and inhibitor design."xsd:string |
| http://purl.uniprot.org/citations/30150473 | http://purl.org/dc/terms/identifier | "doi:10.1128/aac.01579-18"xsd:string |
| http://purl.uniprot.org/citations/30150473 | http://purl.uniprot.org/core/author | "Hao Q."xsd:string |
| http://purl.uniprot.org/citations/30150473 | http://purl.uniprot.org/core/author | "Wang C."xsd:string |
| http://purl.uniprot.org/citations/30150473 | http://purl.uniprot.org/core/author | "Zhang H."xsd:string |
| http://purl.uniprot.org/citations/30150473 | http://purl.uniprot.org/core/author | "Zhao L."xsd:string |
| http://purl.uniprot.org/citations/30150473 | http://purl.uniprot.org/core/author | "Zhu Y."xsd:string |
| http://purl.uniprot.org/citations/30150473 | http://purl.uniprot.org/core/author | "Fang H."xsd:string |
| http://purl.uniprot.org/citations/30150473 | http://purl.uniprot.org/core/author | "Zeng L."xsd:string |
| http://purl.uniprot.org/citations/30150473 | http://purl.uniprot.org/core/author | "Ma G."xsd:string |
| http://purl.uniprot.org/citations/30150473 | http://purl.uniprot.org/core/author | "Pang B."xsd:string |
| http://purl.uniprot.org/citations/30150473 | http://purl.uniprot.org/core/author | "Ahmad A."xsd:string |
| http://purl.uniprot.org/citations/30150473 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/30150473 | http://purl.uniprot.org/core/name | "Antimicrob Agents Chemother"xsd:string |
| http://purl.uniprot.org/citations/30150473 | http://purl.uniprot.org/core/pages | "e01579-18"xsd:string |
| http://purl.uniprot.org/citations/30150473 | http://purl.uniprot.org/core/title | "Active-Site Conformational Fluctuations Promote the Enzymatic Activity of NDM-1."xsd:string |
| http://purl.uniprot.org/citations/30150473 | http://purl.uniprot.org/core/volume | "62"xsd:string |
| http://purl.uniprot.org/citations/30150473 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/30150473 |
| http://purl.uniprot.org/citations/30150473 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/30150473 |
| http://purl.uniprot.org/uniprot/#_C7C422-mappedCitation-30150473 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30150473 |
| http://purl.uniprot.org/uniprot/C7C422 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/30150473 |