| http://purl.uniprot.org/citations/10097070 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/10097070 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/10097070 | http://www.w3.org/2000/01/rdf-schema#comment | "Inosine monophosphate dehydrogenase (IMPDH) controls a key metabolic step in the regulation of cell growth and differentiation. This step is the NAD-dependent oxidation of inosine 5' monophosphate (IMP) to xanthosine 5' monophosphate, the rate-limiting step in the synthesis of the guanine nucleotides. Two isoforms of IMPDH have been identified, one of which (type II) is significantly up-regulated in neoplastic and differentiating cells. As such, it has been identified as a major target in antitumor and immunosuppressive drug design. We present here the 2.9-A structure of a ternary complex of the human type II isoform of IMPDH. The complex contains the substrate analogue 6-chloropurine riboside 5'-monophosphate (6-Cl-IMP) and the NAD analogue selenazole-4-carboxamide adenine dinucleotide, the selenium derivative of the active metabolite of the antitumor drug tiazofurin. The enzyme forms a homotetramer, with the dinucleotide binding at the monomer-monomer interface. The 6 chloro-substituted purine base is dehalogenated, forming a covalent adduct at C6 with Cys-331. The dinucleotide selenazole base is stacked against the 6-Cl-IMP purine ring in an orientation consistent with the B-side stereochemistry of hydride transfer seen with NAD. The adenosine end of the ligand interacts with residues not conserved between the type I and type II isoforms, suggesting strategies for the design of isoform-specific agents."xsd:string |
| http://purl.uniprot.org/citations/10097070 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.96.7.3531"xsd:string |
| http://purl.uniprot.org/citations/10097070 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.96.7.3531"xsd:string |
| http://purl.uniprot.org/citations/10097070 | http://purl.uniprot.org/core/author | "Markham G.D."xsd:string |
| http://purl.uniprot.org/citations/10097070 | http://purl.uniprot.org/core/author | "Markham G.D."xsd:string |
| http://purl.uniprot.org/citations/10097070 | http://purl.uniprot.org/core/author | "Colby T.D."xsd:string |
| http://purl.uniprot.org/citations/10097070 | http://purl.uniprot.org/core/author | "Colby T.D."xsd:string |
| http://purl.uniprot.org/citations/10097070 | http://purl.uniprot.org/core/author | "Goldstein B.M."xsd:string |
| http://purl.uniprot.org/citations/10097070 | http://purl.uniprot.org/core/author | "Goldstein B.M."xsd:string |
| http://purl.uniprot.org/citations/10097070 | http://purl.uniprot.org/core/author | "Strickler M.D."xsd:string |
| http://purl.uniprot.org/citations/10097070 | http://purl.uniprot.org/core/author | "Strickler M.D."xsd:string |
| http://purl.uniprot.org/citations/10097070 | http://purl.uniprot.org/core/author | "Vanderveen K."xsd:string |
| http://purl.uniprot.org/citations/10097070 | http://purl.uniprot.org/core/author | "Vanderveen K."xsd:string |
| http://purl.uniprot.org/citations/10097070 | http://purl.uniprot.org/core/date | "1999"xsd:gYear |
| http://purl.uniprot.org/citations/10097070 | http://purl.uniprot.org/core/date | "1999"xsd:gYear |
| http://purl.uniprot.org/citations/10097070 | http://purl.uniprot.org/core/name | "Proc. Natl. Acad. Sci. U.S.A."xsd:string |
| http://purl.uniprot.org/citations/10097070 | http://purl.uniprot.org/core/name | "Proc. Natl. Acad. Sci. U.S.A."xsd:string |
| http://purl.uniprot.org/citations/10097070 | http://purl.uniprot.org/core/pages | "3531-3536"xsd:string |
| http://purl.uniprot.org/citations/10097070 | http://purl.uniprot.org/core/pages | "3531-3536"xsd:string |
| http://purl.uniprot.org/citations/10097070 | http://purl.uniprot.org/core/title | "Crystal structure of human type II inosine monophosphate dehydrogenase: implications for ligand binding and drug design."xsd:string |
| http://purl.uniprot.org/citations/10097070 | http://purl.uniprot.org/core/title | "Crystal structure of human type II inosine monophosphate dehydrogenase: implications for ligand binding and drug design."xsd:string |
| http://purl.uniprot.org/citations/10097070 | http://purl.uniprot.org/core/volume | "96"xsd:string |
| http://purl.uniprot.org/citations/10097070 | http://purl.uniprot.org/core/volume | "96"xsd:string |