3g3d | pdb_00003g3d

Crystal Structure of Human Orotidine 5'-monophosphate Decarboxylase Covalently Modified by 5-fluoro-6-azido-UMP

spinqualitylabelsall models 3g3d, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3g3d is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 5FU, GOL, SO4 Related: 3g3m Gene: gi|13960142, OK/SW-cl.21, UMPS (HUMAN) Activity: Orotidine-5'-phosphate decarboxylase, with EC number 4.1.1.23 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [UMPS_HUMAN] Defects in UMPS are the cause of orotic aciduria type 1 (ORAC1) [MIM:258900]. A disorder of pyrimidine metabolism resulting in megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. A minority of cases have additional features, particularly congenital malformations and immune deficiencies. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed A series of 6-substituted and 5-fluoro-6-substituted uridine derivatives were synthesized and evaluated for their potential as anticancer agents. The designed molecules were synthesized from either fully protected uridine or the corresponding 5-fluorouridine derivatives. The mononucleotide derivatives were used for enzyme inhibition investigations against ODCase. Anticancer activities of all the synthesized derivatives were evaluated using the nucleoside forms of the inhibitors. 5-Fluoro-UMP was a very weak inhibitor of ODCase. 6-Azido-5-fluoro and 5-fluoro-6-iodo derivatives are covalent inhibitors of ODCase, and the active site Lys145 residue covalently binds to the ligand after the elimination of the 6-substitution. Among the synthesized nucleoside derivatives, 6-azido-5-fluoro, 6-amino-5-fluoro, and 6-carbaldehyde-5-fluoro derivatives showed potent anticancer activities in cell-based assays against various leukemia cell lines. On the basis of the overall profile, 6-azido-5-fluoro and 6-amino-5-fluoro uridine derivatives exhibited potential for further investigations. Structure-activity relationships of orotidine-5'-monophosphate decarboxylase inhibitors as anticancer agents.,Bello AM, Konforte D, Poduch E, Furlonger C, Wei L, Liu Y, Lewis M, Pai EF, Paige CJ, Kotra LP J Med Chem. 2009 Mar 26;52(6):1648-58. PMID:19260677 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Uridine 5'-monophosphate synthase

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