PDBsum entry 3g3d

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protein ligands Protein-protein interface(s) links
Lyase PDB id
Protein chains
256 a.a. *
5FU ×2
GOL ×3
Waters ×331
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Crystal structure of human orotidine 5'-monophosphate decarb covalently modified by 5-fluoro-6-azido-ump
Structure: Uridine 5'-monophosphate synthase. Chain: a, b. Fragment: unp residues 190-480, orotidine 5'-phosphate deca domain. Synonym: ump synthase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: gi|13960142, ok/sw-cl.21, umps. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.70Å     R-factor:   0.177     R-free:   0.210
Authors: Y.Liu,H.L.Tang,A.Bello,E.Poduch,L.Kotra,E.Pai
Key ref: A.M.Bello et al. (2009). Structure-activity relationships of orotidine-5'-monophosphate decarboxylase inhibitors as anticancer agents. J Med Chem, 52, 1648-1658. PubMed id: 19260677
02-Feb-09     Release date:   03-Mar-09    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P11172  (UMPS_HUMAN) -  Uridine 5'-monophosphate synthase
480 a.a.
256 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: E.C.  - Orotate phosphoribosyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Pyrimidine Biosynthesis
      Reaction: Orotidine 5'-phosphate + diphosphate = orotate + 5-phospho-alpha-D-ribose 1-diphosphate
Orotidine 5'-phosphate
Bound ligand (Het Group name = 5FU)
matches with 84.00% similarity
+ diphosphate
= orotate
+ 5-phospho-alpha-D-ribose 1-diphosphate
   Enzyme class 2: E.C.  - Orotidine-5'-phosphate decarboxylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Reaction: Orotidine 5'-phosphate = UMP + CO2
Orotidine 5'-phosphate
Bound ligand (Het Group name = 5FU)
matches with 95.45% similarity
+ CO(2)
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   3 terms 
  Biochemical function     catalytic activity     2 terms  


J Med Chem 52:1648-1658 (2009)
PubMed id: 19260677  
Structure-activity relationships of orotidine-5'-monophosphate decarboxylase inhibitors as anticancer agents.
A.M.Bello, D.Konforte, E.Poduch, C.Furlonger, L.Wei, Y.Liu, M.Lewis, E.F.Pai, C.J.Paige, L.P.Kotra.
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.