| http://purl.uniprot.org/citations/12771141 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12771141 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12771141 | http://www.w3.org/2000/01/rdf-schema#comment | "Synercid, a new semisynthetic streptogramin-derived antibiotic containing dalfopristin and quinupristin, is used in treatment of life-threatening infections caused by glycopeptide-resistant Enterococcus faecium and other bacterial pathogens. However, dissemination of genes encoding virginiamycin acetyltransferases, enzymes that confer resistance to streptogramins, threatens to limit the medical utility of the quinupristin-dalfopristin combination. Here we present structures of virginiamycin acetyltransferase D (VatD) determined at 1.8 A resolution in the absence of ligands, at 2.8 A resolution bound to dalfopristin, and at 3.0 A resolution in the presence of acetyl-coenzyme A. Dalfopristin is bound by VatD in a similar conformation to that described previously for the streptogramin virginiamycin M1. However, specific interactions with the substrate are altered as a consequence of a conformational change in the pyrollidine ring that is propagated to adjacent constituents of the dalfopristin macrocycle. Inactivation of dalfopristin involves acetyl transfer from acetyl-coenzyme A to the sole (O-18) hydroxy group of the antibiotic that lies close to the side chain of the strictly conserved residue, His-82. Replacement of residue 82 by alanine is accompanied by a fall in specific activity of >105-fold, indicating that the imidazole moiety of His-82 is a major determinant of catalytic rate enhancement by VatD. The structure of the VatD-dalfopristin complex can be used to predict positions where further structural modification of the drug might preclude enzyme binding and thereby circumvent Synercid resistance."xsd:string |
| http://purl.uniprot.org/citations/12771141 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m303766200"xsd:string |
| http://purl.uniprot.org/citations/12771141 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m303766200"xsd:string |
| http://purl.uniprot.org/citations/12771141 | http://purl.uniprot.org/core/author | "Courvalin P."xsd:string |
| http://purl.uniprot.org/citations/12771141 | http://purl.uniprot.org/core/author | "Courvalin P."xsd:string |
| http://purl.uniprot.org/citations/12771141 | http://purl.uniprot.org/core/author | "Rafferty J.B."xsd:string |
| http://purl.uniprot.org/citations/12771141 | http://purl.uniprot.org/core/author | "Rafferty J.B."xsd:string |
| http://purl.uniprot.org/citations/12771141 | http://purl.uniprot.org/core/author | "Murray I.A."xsd:string |
| http://purl.uniprot.org/citations/12771141 | http://purl.uniprot.org/core/author | "Murray I.A."xsd:string |
| http://purl.uniprot.org/citations/12771141 | http://purl.uniprot.org/core/author | "Kehoe L.E."xsd:string |
| http://purl.uniprot.org/citations/12771141 | http://purl.uniprot.org/core/author | "Kehoe L.E."xsd:string |
| http://purl.uniprot.org/citations/12771141 | http://purl.uniprot.org/core/author | "Snidwongse J."xsd:string |
| http://purl.uniprot.org/citations/12771141 | http://purl.uniprot.org/core/author | "Snidwongse J."xsd:string |
| http://purl.uniprot.org/citations/12771141 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/12771141 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/12771141 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/12771141 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/12771141 | http://purl.uniprot.org/core/pages | "29963-29970"xsd:string |
| http://purl.uniprot.org/citations/12771141 | http://purl.uniprot.org/core/pages | "29963-29970"xsd:string |
| http://purl.uniprot.org/citations/12771141 | http://purl.uniprot.org/core/title | "Structural basis of Synercid (quinupristin-dalfopristin) resistance in Gram-positive bacterial pathogens."xsd:string |
| http://purl.uniprot.org/citations/12771141 | http://purl.uniprot.org/core/title | "Structural basis of Synercid (quinupristin-dalfopristin) resistance in Gram-positive bacterial pathogens."xsd:string |
| http://purl.uniprot.org/citations/12771141 | http://purl.uniprot.org/core/volume | "278"xsd:string |
| http://purl.uniprot.org/citations/12771141 | http://purl.uniprot.org/core/volume | "278"xsd:string |