PDBsum entry 1z35

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Transferase PDB id
Protein chain
230 a.a. *
Waters ×76
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of trichomonas vaginalis purine nucleoside phosphorylase complexed with 2-fluoroadenosine
Structure: Purine nucleoside phosphorylase. Chain: a. Engineered: yes
Source: Trichomonas vaginalis. Organism_taxid: 5722. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Hexamer (from PDB file)
2.50Å     R-factor:   0.204     R-free:   0.244
Authors: Y.Zhang,W.H.Wang,S.W.Wu,C.C.Wang,S.E.Ealick
Key ref:
Y.Zang et al. (2005). Identification of a subversive substrate of Trichomonas vaginalis purine nucleoside phosphorylase and the crystal structure of the enzyme-substrate complex. J Biol Chem, 280, 22318-22325. PubMed id: 15817485 DOI: 10.1074/jbc.M501843200
10-Mar-05     Release date:   29-Mar-05    
Go to PROCHECK summary

Protein chain
No UniProt id for this chain
Struc: 230 a.a.
Key:    Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Purine-nucleoside phosphorylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
1. Purine nucleoside + phosphate = purine + alpha-D-ribose 1-phosphate
2. Purine deoxynucleoside + phosphate = purine + 2'-deoxy-alpha-D-ribose 1-phosphate
Purine nucleoside
Bound ligand (Het Group name = 2FA)
matches with 90.00% similarity
+ phosphate
= purine
+ alpha-D-ribose 1-phosphate
Purine deoxynucleoside
+ phosphate
= purine
+ 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     nucleobase-containing compound metabolic process   2 terms 
  Biochemical function     catalytic activity     2 terms  


DOI no: 10.1074/jbc.M501843200 J Biol Chem 280:22318-22325 (2005)
PubMed id: 15817485  
Identification of a subversive substrate of Trichomonas vaginalis purine nucleoside phosphorylase and the crystal structure of the enzyme-substrate complex.
Y.Zang, W.H.Wang, S.W.Wu, S.E.Ealick, C.C.Wang.
Trichomonas vaginalis is an anaerobic protozoan parasite that causes trichomoniasis, a common sexually transmitted disease with worldwide impact. One of the pivotal enzymes in its purine salvage pathway, purine nucleoside phosphorylase (PNP), shows physical properties and substrate specificities similar to those of the high molecular mass bacterial PNPs but differing from those of human PNP. While carrying out studies to identify inhibitors of T. vaginalis PNP (TvPNP), we discovered that the nontoxic nucleoside analogue 2-fluoro-2'-deoxyadenosine (F-dAdo) is a "subversive substrate." Phosphorolysis by TvPNP of F-dAdo, which is not a substrate for human PNP, releases highly cytotoxic 2-fluoroadenine (F-Ade). In vitro studies showed that both F-dAdo and F-Ade exert strong inhibition of T. vaginalis growth with estimated IC(50) values of 106 and 84 nm, respectively, suggesting that F-dAdo might be useful as a potential chemotherapeutic agent against T. vaginalis. To understand the basis of TvPNP specificity, the structures of TvPNP complexed with F-dAdo, 2-fluoroadenosine, formycin A, adenosine, inosine, or 2'-deoxyinosine were determined by x-ray crystallography with resolutions ranging from 2.4 to 2.9 A. These studies showed that the quaternary structure, monomer fold, and active site are similar to those of Escherichia coli PNP. The principal active site difference is at Thr-156, which is alanine in E. coli PNP. In the complex of TvPNP with F-dAdo, Thr-156 causes the purine base to tilt and shift by 0.5 A as compared with the binding scheme of F-dAdo in E. coli PNP. The structures of the TvPNP complexes suggest opportunities for further improved subversive substrates beyond F-dAdo.
  Selected figure(s)  
Figure 1.
FIG. 1. Structures of the nucleoside ligands bound to TvPNP. IUPAC numbering conventions differ for the purine and formycin ring systems. The purine numbering system, shown for adenosine, is used throughout the paper for consistency. TvPNP recognizes adenosine, inosine, and guanosine as natural substrates, of which adenosine is the most efficient substrate.
Figure 7.
FIG. 7. Schematic diagram of the active site. A, the F-dAdo complex. B, the FMA complex.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 22318-22325) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20532912 J.M.Wright, L.A.Dunn, Z.Kazimierczuk, A.G.Burgess, K.G.Krauer, P.Upcroft, and J.A.Upcroft (2010).
Susceptibility in vitro of clinically metronidazole-resistant Trichomonas vaginalis to nitazoxanide, toyocamycin, and 2-fluoro-2'-deoxyadenosine.
  Parasitol Res, 107, 847-853.  
19139128 S.Afshar, T.Asai, and S.L.Morrison (2009).
Humanized ADEPT comprised of an engineered human purine nucleoside phosphorylase and a tumor targeting peptide for treatment of cancer.
  Mol Cancer Ther, 8, 185-193.  
17223688 A.Rinaldo-Matthis, C.Wing, M.Ghanem, H.Deng, P.Wu, A.Gupta, P.C.Tyler, G.B.Evans, R.H.Furneaux, S.C.Almo, C.C.Wang, and V.L.Schramm (2007).
Inhibition and structure of Trichomonas vaginalis purine nucleoside phosphorylase with picomolar transition state analogues.
  Biochemistry, 46, 659-668.
PDB codes: 2i4t 2isc
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