3G3D
Crystal Structure of Human Orotidine 5'-monophosphate Decarboxylase Covalently Modified by 5-fluoro-6-azido-UMP
Summary for 3G3D
| Entry DOI | 10.2210/pdb3g3d/pdb |
| Related | 3G3M |
| Descriptor | Uridine 5'-monophosphate synthase, 5-FLUORO-URIDINE-5'-MONOPHOSPHATE, GLYCEROL, ... (5 entities in total) |
| Functional Keywords | ump synthase, c-terminal domain, orotidine 5'-monophosphate decarboxylase, human, 5-fluoro-6-azido-ump, decarboxylase, disease mutation, glycosyltransferase, lyase, multifunctional enzyme, phosphoprotein, pyrimidine biosynthesis, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 69165.00 |
| Authors | Liu, Y.,Tang, H.L.,Bello, A.,Poduch, E.,Kotra, L.,Pai, E. (deposition date: 2009-02-02, release date: 2009-03-03, Last modification date: 2024-10-09) |
| Primary citation | Bello, A.M.,Konforte, D.,Poduch, E.,Furlonger, C.,Wei, L.,Liu, Y.,Lewis, M.,Pai, E.F.,Paige, C.J.,Kotra, L.P. Structure-activity relationships of orotidine-5'-monophosphate decarboxylase inhibitors as anticancer agents. J.Med.Chem., 52:1648-1658, 2009 Cited by PubMed Abstract: 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. PubMed: 19260677DOI: 10.1021/jm801224t PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
Download full validation report
