| http://purl.uniprot.org/citations/21359640 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21359640 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21359640 | http://www.w3.org/2000/01/rdf-schema#comment | "As part of the Seattle Structural Genomics Center for Infectious Disease, we seek to enhance structural genomics with ligand-bound structure data which can serve as a blueprint for structure-based drug design. We have adapted fragment-based screening methods to our structural genomics pipeline to generate multiple ligand-bound structures of high priority drug targets from pathogenic organisms. In this study, we report fragment screening methods and structure determination results for 2C-methyl-D-erythritol-2,4-cyclo-diphosphate (MECP) synthase from Burkholderia pseudomallei, the gram-negative bacterium which causes melioidosis. Screening by nuclear magnetic resonance spectroscopy as well as crystal soaking followed by X-ray diffraction led to the identification of several small molecules which bind this enzyme in a critical metabolic pathway. A series of complex structures obtained with screening hits reveal distinct binding pockets and a range of small molecules which form complexes with the target. Additional soaks with these compounds further demonstrate a subset of fragments to only bind the protein when present in specific combinations. This ensemble of fragment-bound complexes illuminates several characteristics of MECP synthase, including a previously unknown binding surface external to the catalytic active site. These ligand-bound structures now serve to guide medicinal chemists and structural biologists in rational design of novel inhibitors for this enzyme."xsd:string |
| http://purl.uniprot.org/citations/21359640 | http://purl.org/dc/terms/identifier | "doi:10.1007/s10969-011-9102-6"xsd:string |
| http://purl.uniprot.org/citations/21359640 | http://purl.org/dc/terms/identifier | "doi:10.1007/s10969-011-9102-6"xsd:string |
| http://purl.uniprot.org/citations/21359640 | http://purl.uniprot.org/core/author | "Abendroth J."xsd:string |
| http://purl.uniprot.org/citations/21359640 | http://purl.uniprot.org/core/author | "Abendroth J."xsd:string |
| http://purl.uniprot.org/citations/21359640 | http://purl.uniprot.org/core/author | "Myler P.J."xsd:string |
| http://purl.uniprot.org/citations/21359640 | http://purl.uniprot.org/core/author | "Myler P.J."xsd:string |
| http://purl.uniprot.org/citations/21359640 | http://purl.uniprot.org/core/author | "Edwards T.E."xsd:string |
| http://purl.uniprot.org/citations/21359640 | http://purl.uniprot.org/core/author | "Edwards T.E."xsd:string |
| http://purl.uniprot.org/citations/21359640 | http://purl.uniprot.org/core/author | "Staker B.L."xsd:string |
| http://purl.uniprot.org/citations/21359640 | http://purl.uniprot.org/core/author | "Staker B.L."xsd:string |
| http://purl.uniprot.org/citations/21359640 | http://purl.uniprot.org/core/author | "Stewart L.J."xsd:string |
| http://purl.uniprot.org/citations/21359640 | http://purl.uniprot.org/core/author | "Stewart L.J."xsd:string |
| http://purl.uniprot.org/citations/21359640 | http://purl.uniprot.org/core/author | "Bhandari J."xsd:string |
| http://purl.uniprot.org/citations/21359640 | http://purl.uniprot.org/core/author | "Bhandari J."xsd:string |
| http://purl.uniprot.org/citations/21359640 | http://purl.uniprot.org/core/author | "Davies D.R."xsd:string |
| http://purl.uniprot.org/citations/21359640 | http://purl.uniprot.org/core/author | "Davies D.R."xsd:string |
| http://purl.uniprot.org/citations/21359640 | http://purl.uniprot.org/core/author | "Begley D.W."xsd:string |
| http://purl.uniprot.org/citations/21359640 | http://purl.uniprot.org/core/author | "Begley D.W."xsd:string |
| http://purl.uniprot.org/citations/21359640 | http://purl.uniprot.org/core/author | "Burris C.A."xsd:string |
| http://purl.uniprot.org/citations/21359640 | http://purl.uniprot.org/core/author | "Burris C.A."xsd:string |
| http://purl.uniprot.org/citations/21359640 | http://purl.uniprot.org/core/author | "Hartley R.C."xsd:string |
| http://purl.uniprot.org/citations/21359640 | http://purl.uniprot.org/core/author | "Hartley R.C."xsd:string |