| http://purl.uniprot.org/citations/18184586 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18184586 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18184586 | http://www.w3.org/2000/01/rdf-schema#comment | "UMP synthase (UMPS) catalyzes the last two steps of de novo pyrimidine nucleotide synthesis and is a potential cancer drug target. The C-terminal domain of UMPS is orotidine-5'-monophosphate decarboxylase (OMPD), a cofactor-less yet extremely efficient enzyme. Studies of OMPDs from micro-organisms led to the proposal of several noncovalent decarboxylation mechanisms via high-energy intermediates. We describe nine crystal structures of human OMPD in complex with substrate, product, and nucleotide inhibitors. Unexpectedly, simple compounds can replace the natural nucleotides and induce a closed conformation of OMPD, defining a tripartite catalytic site. The structures outline the requirements drugs must meet to maximize therapeutic effects and minimize cross-species activity. Chemical mimicry by iodide identified a CO(2) product binding site. Plasticity of catalytic residues and a covalent OMPD-UMP complex prompt a reevaluation of the prevailing decarboxylation mechanism in favor of covalent intermediates. This mechanism can also explain the observed catalytic promiscuity of OMPD."xsd:string |
| http://purl.uniprot.org/citations/18184586 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.str.2007.10.020"xsd:string |
| http://purl.uniprot.org/citations/18184586 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.str.2007.10.020"xsd:string |
| http://purl.uniprot.org/citations/18184586 | http://purl.uniprot.org/core/author | "Rudolph M.G."xsd:string |
| http://purl.uniprot.org/citations/18184586 | http://purl.uniprot.org/core/author | "Rudolph M.G."xsd:string |
| http://purl.uniprot.org/citations/18184586 | http://purl.uniprot.org/core/author | "Frey A."xsd:string |
| http://purl.uniprot.org/citations/18184586 | http://purl.uniprot.org/core/author | "Frey A."xsd:string |
| http://purl.uniprot.org/citations/18184586 | http://purl.uniprot.org/core/author | "Gasow K."xsd:string |
| http://purl.uniprot.org/citations/18184586 | http://purl.uniprot.org/core/author | "Gasow K."xsd:string |
| http://purl.uniprot.org/citations/18184586 | http://purl.uniprot.org/core/author | "Wittmann J.G."xsd:string |
| http://purl.uniprot.org/citations/18184586 | http://purl.uniprot.org/core/author | "Wittmann J.G."xsd:string |
| http://purl.uniprot.org/citations/18184586 | http://purl.uniprot.org/core/author | "Diederichsen U."xsd:string |
| http://purl.uniprot.org/citations/18184586 | http://purl.uniprot.org/core/author | "Diederichsen U."xsd:string |
| http://purl.uniprot.org/citations/18184586 | http://purl.uniprot.org/core/author | "Heinrich D."xsd:string |
| http://purl.uniprot.org/citations/18184586 | http://purl.uniprot.org/core/author | "Heinrich D."xsd:string |
| http://purl.uniprot.org/citations/18184586 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18184586 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18184586 | http://purl.uniprot.org/core/name | "Structure"xsd:string |
| http://purl.uniprot.org/citations/18184586 | http://purl.uniprot.org/core/name | "Structure"xsd:string |
| http://purl.uniprot.org/citations/18184586 | http://purl.uniprot.org/core/pages | "82-92"xsd:string |
| http://purl.uniprot.org/citations/18184586 | http://purl.uniprot.org/core/pages | "82-92"xsd:string |
| http://purl.uniprot.org/citations/18184586 | http://purl.uniprot.org/core/title | "Structures of the human orotidine-5'-monophosphate decarboxylase support a covalent mechanism and provide a framework for drug design."xsd:string |
| http://purl.uniprot.org/citations/18184586 | http://purl.uniprot.org/core/title | "Structures of the human orotidine-5'-monophosphate decarboxylase support a covalent mechanism and provide a framework for drug design."xsd:string |