PDBsum entry 1pwy

Go to PDB code: 
protein ligands links
Transferase PDB id
Protein chain
288 a.a. *
SO4 ×3
Waters ×43
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of human pnp complexed with acyclovir
Structure: Purine nucleoside phosphorylase. Chain: e. Synonym: inosine phosphorylase, pnp. Engineered: yes. Other_details: complexed with acyclovir
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: pnp. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Trimer (from PDB file)
2.80Å     R-factor:   0.215     R-free:   0.301
Authors: D.M.Dos Santos,F.Canduri,J.H.Pereira,M.Vinicius Bertacine Di R.G.Silva,M.A.Mendes,M.S.Palma,L.A.Basso,W.F.De Azevedo,D.S
Key ref: D.M.dos Santos et al. (2003). Crystal structure of human purine nucleoside phosphorylase complexed with acyclovir. Biochem Biophys Res Commun, 308, 553-559. PubMed id: 12914786 DOI: 10.1016/S0006-291X(03)01433-5
02-Jul-03     Release date:   23-Mar-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P00491  (PNPH_HUMAN) -  Purine nucleoside phosphorylase
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.  - 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 = AC2)
matches with 70.00% 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!
  Cellular component     intracellular   5 terms 
  Biological process     small molecule metabolic process   16 terms 
  Biochemical function     catalytic activity     9 terms  


DOI no: 10.1016/S0006-291X(03)01433-5 Biochem Biophys Res Commun 308:553-559 (2003)
PubMed id: 12914786  
Crystal structure of human purine nucleoside phosphorylase complexed with acyclovir.
D.M.dos Santos, F.Canduri, J.H.Pereira, M.Vinicius Bertacine Dias, R.G.Silva, M.A.Mendes, M.S.Palma, L.A.Basso, Azevedo, D.S.Santos.
In human, purine nucleoside phosphorylase (HsPNP) is responsible for degradation of deoxyguanosine and genetic deficiency of this enzyme leads to profound T-cell mediated immunosuppression. PNP is therefore a target for inhibitor development aiming at T-cell immune response modulation and has been submitted to extensive structure-based drug design. This work reports the first crystallographic study of human PNP complexed with acyclovir (HsPNP:Acy). Acyclovir is a potent clinically useful inhibitor of replicant herpes simplex virus that also inhibits human PNP but with a relatively lower inhibitory activity (K(i)=90 microM). Analysis of the structural differences among the HsPNP:Acy complex, PNP apoenzyme, and HsPNP:Immucillin-H provides explanation for inhibitor binding, refines the purine-binding site, and can be used for future inhibitor design.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20799866 A.Al-Kali, V.Gandhi, M.Ayoubi, M.Keating, and F.Ravandi (2010).
Forodesine: review of preclinical and clinical data.
  Future Oncol, 6, 1211-1217.  
19669809 F.B.Zanchi, R.A.Caceres, R.G.Stabeli, and Azevedo (2010).
Molecular dynamics studies of a hexameric purine nucleoside phosphorylase.
  J Mol Model, 16, 543-550.  
20442367 K.Balakrishnan, J.A.Burger, M.P.Quiroga, M.Henneberg, M.L.Ayres, W.G.Wierda, and V.Gandhi (2010).
Influence of bone marrow stromal microenvironment on forodesine-induced responses in CLL primary cells.
  Blood, 116, 1083-1091.  
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 Azevedo (2009).
Molecular modeling and dynamics studies of purine nucleoside phosphorylase from Bacteroides fragilis.
  J Mol Model, 15, 913-922.  
17107284 F.Ravandi, and V.Gandhi (2006).
Novel purine nucleoside analogues for T-cell-lineage acute lymphoblastic leukaemia and lymphoma.
  Expert Opin Investig Drugs, 15, 1601-1613.  
15983407 F.Canduri, R.G.Silva, D.M.dos Santos, M.S.Palma, L.A.Basso, D.S.Santos, and Azevedo (2005).
Structure of human PNP complexed with ligands.
  Acta Crystallogr D Biol Crystallogr, 61, 856-862.
PDB codes: 1rfg 1v41 1v45
16131572 V.Gandhi, J.M.Kilpatrick, W.Plunkett, M.Ayres, L.Harman, M.Du, S.Bantia, J.Davisson, W.G.Wierda, S.Faderl, H.Kantarjian, and D.Thomas (2005).
A proof-of-principle pharmacokinetic, pharmacodynamic, and clinical study with purine nucleoside phosphorylase inhibitor immucillin-H (BCX-1777, forodesine).
  Blood, 106, 4253-4260.  
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.