PDBsum entry 1brw

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protein ligands metals Protein-protein interface(s) links
Transferase PDB id
Jmol PyMol
Protein chains
433 a.a. *
PO4 ×2
MES ×2
_CA ×2
Waters ×110
* Residue conservation analysis
PDB id:
Name: Transferase
Title: The crystal structure of pyrimidine nucleoside phosphorylase in a closed conformation
Structure: Protein (pyrimidine nucleoside phosphorylase). Chain: a, b. Synonym: pynp. Ec:
Source: Geobacillus stearothermophilus. Organism_taxid: 1422
2.10Å     R-factor:   0.232     R-free:   0.276
Authors: M.J.Pugmire,S.E.Ealick
Key ref:
M.J.Pugmire and S.E.Ealick (1998). The crystal structure of pyrimidine nucleoside phosphorylase in a closed conformation. Structure, 6, 1467-1479. PubMed id: 9817849 DOI: 10.1016/S0969-2126(98)00145-2
25-Aug-98     Release date:   13-Jan-99    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P77836  (PDP_GEOSE) -  Pyrimidine-nucleoside phosphorylase
433 a.a.
433 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 100 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - Pyrimidine-nucleoside phosphorylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
1. Uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
2. Thymidine + phosphate = thymine + 2-deoxy-alpha-D-ribose 1-phosphate
3. 2'-deoxyuridine + phosphate = uracil + 2-deoxy-alpha-D-ribose 1-phosphate
Bound ligand (Het Group name = PO4)
corresponds exactly
Bound ligand (Het Group name = URA)
matches with 75.00% similarity
+ alpha-D-ribose 1-phosphate
+ phosphate
= thymine
+ 2-deoxy-alpha-D-ribose 1-phosphate
+ phosphate
= uracil
+ 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!
  Biological process     metabolic process   3 terms 
  Biochemical function     transferase activity     6 terms  


DOI no: 10.1016/S0969-2126(98)00145-2 Structure 6:1467-1479 (1998)
PubMed id: 9817849  
The crystal structure of pyrimidine nucleoside phosphorylase in a closed conformation.
M.J.Pugmire, S.E.Ealick.
BACKGROUND: Pyrimidine nucleoside phosphorylase (PYNP) catalyzes the reversible phosphorolysis of pyrimidines in the nucleotide synthesis salvage pathway. In lower organisms (e.g. Bacillus stearothermophilus) PYNP accepts both thymidine and uridine, whereas in mammalian and other higher organisms it is specific for thymidine (designated thymidine phosphorylase, TP). PYNP shares 40% sequence similarity (and presumably significant structural similarity) with human TP, which has been implicated as a growth factor in tumor angiogenesis. It is thought that TP undergoes a major conformational change upon substrate binding that consequently produces an active conformation. RESULTS: The crystal structure of PYNP from B. stearothermophilus with the substrate analog pseudouridine in its active site has been solved to 2.1 A resolution. This structure confirms the similarity of PYNP to TP and supports the idea of a closed active conformation, which is the result of rigid body movement of the alpha and alpha/beta domains. The active-site cleft, where the pyrimidine and phosphate substrates bind, is between the two domains. The structure reveals an asymmetric dimer in which one subunit is fully closed and the other is only partially closed. CONCLUSIONS: The closed conformation of PYNP serves as a good model to better understand the domain movement and overall function of TP. Active-site residues are confirmed and a possible mechanism for substrate binding and subsequent domain movement is suggested. Potent inhibitors of TP might have significant therapeutic value in various chemotherapeutic strategies, and the structure of PYNP should provide valuable insight into the rational design of such inhibitors.
  Selected figure(s)  
Figure 5.
Figure 5. Schematic drawing of the active-site contacts seen in subunit B of PYNP. Hydrogen bonds are shown as dashed lines and distances are indicated in . The position of the ribose moiety, not observed experimentally, has been modeled. The drawing was produced using CHEMDRAW (CambridgeSoft, Cambridge, MA).
  The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 1467-1479) copyright 1998.  
  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.  
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
15983408 W.Bu, E.C.Settembre, M.H.el Kouni, and S.E.Ealick (2005).
Structural basis for inhibition of Escherichia coli uridine phosphorylase by 5-substituted acyclouridines.
  Acta Crystallogr D Biol Crystallogr, 61, 863-872.
PDB codes: 1u1c 1u1d 1u1e 1u1f 1u1g
14725767 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, and R.A.Pauptit (2004).
Crystal structure of human thymidine phosphorylase in complex with a small molecule inhibitor.
  Structure, 12, 75-84.
PDB code: 1uou
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.  
12093726 O.Mayans, A.Ivens, L.J.Nissen, K.Kirschner, and M.Wilmanns (2002).
Structural analysis of two enzymes catalysing reverse metabolic reactions implies common ancestry.
  EMBO J, 21, 3245-3254.
PDB codes: 1gxb 1o17
11489901 T.C.Appleby, I.I.Mathews, M.Porcelli, G.Cacciapuoti, and S.E.Ealick (2001).
Three-dimensional structure of a hyperthermophilic 5'-deoxy-5'-methylthioadenosine phosphorylase from Sulfolobus solfataricus.
  J Biol Chem, 276, 39232-39242.
PDB codes: 1jds 1jdt 1jdu 1jdv 1jdz 1je0 1je1 1jp7 1jpv
10931945 C.D.Wolfgang, M.Essand, J.J.Vincent, B.Lee, and I.Pastan (2000).
TARP: a nuclear protein expressed in prostate and breast cancer cells derived from an alternate reading frame of the T cell receptor gamma chain locus.
  Proc Natl Acad Sci U S A, 97, 9437-9442.  
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.