PDBsum entry 1uou

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Transferase PDB id
Protein chain
438 a.a. *
Waters ×75
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of human thymidine phosphorylase in complex with a small molecule inhibitor
Structure: Thymidine phosphorylase. Chain: a. Fragment: residues 12-408,411-482. Synonym: tdrpase, tp, platelet-derived endothelial cell growth factor, pd-ecgf, gliostatin. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PDB file)
2.11Å     R-factor:   0.192     R-free:   0.258
Authors: R.A.Norman,S.T.Barry,M.Bate,J.Breed,J.G.Colls,R.J.Ernill, R.W.A.Luke,C.A.Minshull,M.S.B.Mcalister,E.J.Mccall, H.H.J.Mcmiken,D.S.Paterson,D.Timms,J.A.Tucker,R.A.Pauptit
Key ref:
R.A.Norman et al. (2004). Crystal structure of human thymidine phosphorylase in complex with a small molecule inhibitor. Structure, 12, 75-84. PubMed id: 14725767 DOI: 10.1016/j.str.2003.11.018
23-Sep-03     Release date:   22-Jan-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P19971  (TYPH_HUMAN) -  Thymidine phosphorylase
482 a.a.
438 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Thymidine phosphorylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Thymidine + phosphate = thymine + 2-deoxy-alpha-D-ribose 1-phosphate
Bound ligand (Het Group name = CMU)
matches with 50.00% similarity
+ phosphate
= thymine
+ 2-deoxy-alpha-D-ribose 1-phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytosol   1 term 
  Biological process     metabolic process   14 terms 
  Biochemical function     transferase activity     8 terms  


DOI no: 10.1016/j.str.2003.11.018 Structure 12:75-84 (2004)
PubMed id: 14725767  
Crystal structure of human thymidine phosphorylase in complex with a small molecule inhibitor.
R.A.Norman, S.T.Barry, M.Bate, J.Breed, J.G.Colls, R.J.Ernill, R.W.Luke, C.A.Minshull, M.S.McAlister, E.J.McCall, H.H.McMiken, D.S.Paterson, D.Timms, J.A.Tucker, R.A.Pauptit.
Human thymidine phosphorylase (HTP), also known as platelet-derived endothelial cell growth factor (PD-ECGF), is overexpressed in certain solid tumors where it is linked to poor prognosis. HTP expression is utilized for certain chemotherapeutic strategies and is also thought to play a role in tumor angiogenesis. We determined the structure of HTP bound to the small molecule uracil hydrochloride (TPI). The inhibitor appears to mimic the substrate transition state, which may help explain the potency of this inhibitor and the catalytic mechanism of pyrimidine nucleotide phosphorylases (PYNPs). Further, we have confirmed the validity of the HTP structure as a template for structure-based drug design by predicting binding affinities for TPI and other known HTP inhibitors using in silico docking techniques. This work provides the first structural insight into the binding mode of any inhibitor to this important drug target and forms the basis for designing novel inhibitors for use in anticancer therapy.
  Selected figure(s)  
Figure 2.
Figure 2. Electron Density Corresponding to TPIStereo view of the final 2.1 F[o]-F[c] omit map to within 2 of the inhibitor molecule contoured at 3.0s (cyan). Nitrogen atoms are blue; oxygen atoms, red; chlorine atom, lime green; carbon atoms and bonds, light purple. All molecular graphics were produced using Bobscript (Esnouf, 1999) and Raster3D (Merrit and Murphy, 2003) except Figure 7, which was produced using PyMOL (DeLano, 2002).
  The above figure is reprinted by permission from Cell Press: Structure (2004, 12, 75-84) copyright 2004.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19434693 A.Bronckaers, F.Gago, J.Balzarini, and S.Liekens (2009).
The dual role of thymidine phosphorylase in cancer development and chemotherapy.
  Med Res Rev, 29, 903-953.  
19555658 E.Mitsiki, A.C.Papageorgiou, S.Iyer, N.Thiyagarajan, S.H.Prior, D.Sleep, C.Finnis, and K.R.Acharya (2009).
Structures of native human thymidine phosphorylase and in complex with 5-iodouracil.
  Biochem Biophys Res Commun, 386, 666-670.
PDB codes: 2wk5 2wk6
  17401202 K.Shimizu, and N.Kunishima (2007).
Purification, crystallization and preliminary X-ray diffraction study on pyrimidine nucleoside phosphorylase TTHA1771 from Thermus thermophilus HB8.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 308-310.  
17430637 V.A.McNally, M.Rajabi, A.Gbaj, I.J.Stratford, P.N.Edwards, K.T.Douglas, R.A.Bryce, M.Jaffar, and S.Freeman (2007).
Design, synthesis and enzymatic evaluation of 6-bridged imidazolyluracil derivatives as inhibitors of human thymidine phosphorylase.
  J Pharm Pharmacol, 59, 537-547.  
17869163 V.L.Schramm (2007).
Binding isotope effects: boon and bane.
  Curr Opin Chem Biol, 11, 529-536.  
16714288 M.Marino, M.Deuss, D.I.Svergun, P.V.Konarev, R.Sterner, and O.Mayans (2006).
Structural and mutational analysis of substrate complexation by anthranilate phosphoribosyltransferase from Sulfolobus solfataricus.
  J Biol Chem, 281, 21410-21421.
PDB codes: 1zxy 1zyk 2gvq
16132363 C.P.Landowski, X.Song, P.L.Lorenzi, J.M.Hilfinger, and G.L.Amidon (2005).
Floxuridine amino acid ester prodrugs: enhancing Caco-2 permeability and resistance to glycosidic bond metabolism.
  Pharm Res, 22, 1510-1518.  
15546501 S.Akiyama, T.Furukawa, T.Sumizawa, Y.Takebayashi, Y.Nakajima, S.Shimaoka, and M.Haraguchi (2004).
The role of thymidine phosphorylase, an angiogenic enzyme, in tumor progression.
  Cancer Sci, 95, 851-857.  
15123637 S.Liekens, A.I.Hernández, D.Ribatti, E.De Clercq, M.J.Camarasa, M.J.Pérez-Pérez, and J.Balzarini (2004).
The nucleoside derivative 5'-O-trityl-inosine (KIN59) suppresses thymidine phosphorylase-triggered angiogenesis via a noncompetitive mechanism of action.
  J Biol Chem, 279, 29598-29605.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.