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PDBsum entry 1v45

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protein ligands links
Transferase PDB id
1v45
Jmol
Contents
Protein chain
288 a.a. *
Ligands
SO4 ×3
3DG
Waters ×30
* Residue conservation analysis
PDB id:
1v45
Name: Transferase
Title: Crystal structure of human pnp complexed with 3-deoxyguanosi
Structure: Purine nucleoside phosphorylase. Chain: e. Synonym: inosine phosphorylase, pnp. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Trimer (from PDB file)
Resolution:
2.86Å     R-factor:   0.180     R-free:   0.249
Authors: F.Canduri,D.M.Dos Santos,R.G.Silva,M.A.Mendes,M.S.Palma,W.F. Azevedo Jr.,L.A.Basso,D.S.Santos
Key ref:
F.Canduri et al. (2005). Structure of human PNP complexed with ligands. Acta Crystallogr D Biol Crystallogr, 61, 856-862. PubMed id: 15983407 DOI: 10.1107/S0907444905005421
Date:
10-Nov-03     Release date:   14-Dec-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00491  (PNPH_HUMAN) -  Purine nucleoside phosphorylase
Seq:
Struc:
289 a.a.
288 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.2.4.2.1  - Purine-nucleoside phosphorylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction:
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 = 3DG)
matches with 85.00% similarity
+ phosphate
= purine
+ alpha-D-ribose 1-phosphate
Purine deoxynucleoside
+ phosphate
=
purine
Bound ligand (Het Group name = 3DG)
matches with 47.37% similarity
+ 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     intracellular   5 terms 
  Biological process     small molecule metabolic process   16 terms 
  Biochemical function     catalytic activity     9 terms  

 

 
    reference    
 
 
DOI no: 10.1107/S0907444905005421 Acta Crystallogr D Biol Crystallogr 61:856-862 (2005)
PubMed id: 15983407  
 
 
Structure of human PNP complexed with ligands.
F.Canduri, R.G.Silva, D.M.dos Santos, M.S.Palma, L.A.Basso, D.S.Santos, W.F.de Azevedo.
 
  ABSTRACT  
 
Purine nucleoside phosphorylase (PNP) is a key enzyme in the purine-salvage pathway, which allows cells to utilize preformed bases and nucleosides in order to synthesize nucleotides. PNP is specific for purine nucleosides in the beta-configuration and exhibits a strong preference for purines containing a 6-keto group and ribosyl-containing nucleosides relative to the corresponding analogues. PNP was crystallized in complex with ligands and data collection was performed using synchrotron radiation. This work reports the structure of human PNP in complex with guanosine (at 2.80 A resolution), 3'-deoxyguanosine (at 2.86 A resolution) and 8-azaguanine (at 2.85 A resolution). These structures were compared with the PNP-guanine, PNP-inosine and PNP-immucillin-H complexes solved previously.
 
  Selected figure(s)  
 
Figure 3.
Figure 3 Superposition of PNP apoenzyme with the PNP-guanine complex, showing the gate movement, which involves a helical transformation of residues 257-265 in the transition apoenzyme complex. Movements of the residues Tyr249, His257 and Lys265 and the position of ligand and sulfates can be observed. The figure was generated with the program MOLMOL (Koradi et al., 1996[Koradi, R., Billeter, M. & Wuthrich, K. (1996). J. Mol. Graph. 14, 51-55.]).
Figure 4.
Figure 4 Binding site of human PNP. (a) HsPNP-guanosine, (b) HsPNP-inosine, (c) HsPNP-immucillin-H, (d) HsPNP-3'-deoxyguanosine, (e) HsPNP-8-azaguanine, (f) HsPNP-guanine.
 
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2005, 61, 856-862) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19669809 F.B.Zanchi, R.A.Caceres, R.G.Stabeli, and W.F.de Azevedo (2010).
Molecular dynamics studies of a hexameric purine nucleoside phosphorylase.
  J Mol Model, 16, 543-550.  
20210752 M.L.Bellows, and C.A.Floudas (2010).
Computational methods for de novo protein design and its applications to the human immunodeficiency virus 1, purine nucleoside phosphorylase, ubiquitin specific protease 7, and histone demethylases.
  Curr Drug Targets, 11, 264-278.  
19172318 I.Pauli, L.F.Timmers, R.A.Caceres, L.A.Basso, D.S.Santos, and W.F.de Azevedo (2009).
Molecular modeling and dynamics studies of purine nucleoside phosphorylase from Bacteroides fragilis.
  J Mol Model, 15, 913-922.  
19388075 S.Afshar, M.R.Sawaya, and S.L.Morrison (2009).
Structure of a mutant human purine nucleoside phosphorylase with the prodrug, 2-fluoro-2'-deoxyadenosine and the cytotoxic drug, 2-fluoroadenine.
  Protein Sci, 18, 1107-1114.
PDB codes: 3gb9 3ggs
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.  
  19958550 S.Afshar, T.Olafsen, A.M.Wu, and S.L.Morrison (2009).
Characterization of an engineered human purine nucleoside phosphorylase fused to an anti-her2/neu single chain Fv for use in ADEPT.
  J Exp Clin Cancer Res, 28, 147.  
17266529 J.E.Hyde (2007).
Targeting purine and pyrimidine metabolism in human apicomplexan parasites.
  Curr Drug Targets, 8, 31-47.  
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.