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PDBsum entry 1a9t

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protein ligands links
Transferase PDB id
1a9t
Jmol
Contents
Protein chain
284 a.a. *
Ligands
R1P
HPA
Waters ×56
* Residue conservation analysis
PDB id:
1a9t
Name: Transferase
Title: Bovine purine nucleoside phosphorylase complexed with 9-deaz and phosphate
Structure: Purine nucleoside phosphorylase. Chain: a. Ec: 2.4.2.1
Source: Bos taurus. Cattle. Organism_taxid: 9913. Organ: spleen
Biol. unit: Trimer (from PQS)
Resolution:
2.00Å     R-factor:   0.190    
Authors: C.Mao,W.J.Cook,M.Zhou,A.A.Fedorov,S.C.Almo,S.E.Ealick
Key ref:
C.Mao et al. (1998). Calf spleen purine nucleoside phosphorylase complexed with substrates and substrate analogues. Biochemistry, 37, 7135-7146. PubMed id: 9585525 DOI: 10.1021/bi9723919
Date:
10-Apr-98     Release date:   17-Jun-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P55859  (PNPH_BOVIN) -  Purine nucleoside phosphorylase
Seq:
Struc:
289 a.a.
284 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
+ phosphate
=
purine
Bound ligand (Het Group name = HPA)
matches with 90.00% similarity
+
alpha-D-ribose 1-phosphate
Bound ligand (Het Group name = R1P)
corresponds exactly
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     cytoplasm   2 terms 
  Biological process     nucleobase-containing compound metabolic process   2 terms 
  Biochemical function     catalytic activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi9723919 Biochemistry 37:7135-7146 (1998)
PubMed id: 9585525  
 
 
Calf spleen purine nucleoside phosphorylase complexed with substrates and substrate analogues.
C.Mao, W.J.Cook, M.Zhou, A.A.Federov, S.C.Almo, S.E.Ealick.
 
  ABSTRACT  
 
Purine nucleoside phosphorylase (PNP) is a key enzyme in the purine salvage pathway, which provides an alternative to the de novo pathway for the biosynthesis of purine nucleotides. PNP catalyzes the reversible phosphorolysis of 2'-deoxypurine ribonucleosides to the free bases and 2-deoxyribose 1-phosphate. Absence of PNP activity in humans is associated with specific T-cell immune suppression. Its key role in these two processes has made PNP an important drug design target. We have investigated the structural details of the PNP-catalyzed reaction by determining the structures of bovine PNP complexes with various substrates and substrate analogues. The preparation of phosphate-free crystals of PNP has allowed us to analyze several novel complexes, including the ternary complex of PNP, purine base, and ribose 1-phosphate and of the completely unbound PNP. These results provide an atomic view for the catalytic mechanism for PNP proposed by M. D. Erion et al. [(1997) Biochemistry 36, 11735-11748], in which an oxocarbenium intermediate is stabilized by phosphate and the negative charge on the purine base is stabilized by active site residues. The bovine PNP structure reveals several new details of substrate and inhibitor binding, including two phosphate-induced conformational changes involving residues 33-36 and 56-69 and a previously undetected role for His64 in phosphate binding. In addition, a well-ordered water molecule is found in the PNP active site when purine base or nucleoside is also present. In contrast to human PNP, only one phosphate binding site was observed. Although binary complexes were observed for nucleoside, purine base, or phosphate, ribose 1-phosphate binding occurs only in the presence of purine base.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21169694 H.D'Muniz Pereira, G.Oliva, and R.C.Garratt (2011).
Purine nucleoside phosphorylase from Schistosoma mansoni in complex with ribose-1-phosphate.
  J Synchrotron Radiat, 18, 62-65.
PDB code: 3fb1
20108972 A.A.Edwards, J.D.Tipton, M.D.Brenowitz, M.R.Emmett, A.G.Marshall, G.B.Evans, P.C.Tyler, and V.L.Schramm (2010).
Conformational states of human purine nucleoside phosphorylase at rest, at work, and with transition state analogues.
  Biochemistry, 49, 2058-2067.  
20063024 D.F.Visser, F.Hennessy, K.Rashamuse, M.E.Louw, and D.Brady (2010).
Cloning, purification and characterisation of a recombinant purine nucleoside phosphorylase from Bacillus halodurans Alk36.
  Extremophiles, 14, 185-192.  
20364833 D.Paul, S.E.O'Leary, K.Rajashankar, W.Bu, A.Toms, E.C.Settembre, J.M.Sanders, T.P.Begley, and S.E.Ealick (2010).
Glycal formation in crystals of uridine phosphorylase.
  Biochemistry, 49, 3499-3509.
PDB codes: 3ku4 3kuk 3kvr 3kvv 3kvy
20124695 Y.N.Kang, Y.Zhang, P.W.Allan, W.B.Parker, J.W.Ting, C.Y.Chang, and S.E.Ealick (2010).
Structure of grouper iridovirus purine nucleoside phosphorylase.
  Acta Crystallogr D Biol Crystallogr, 66, 155-162.
PDB code: 3khs
19425594 A.A.Edwards, J.M.Mason, K.Clinch, P.C.Tyler, G.B.Evans, and V.L.Schramm (2009).
Altered enthalpy-entropy compensation in picomolar transition state analogues of human purine nucleoside phosphorylase.
  Biochemistry, 48, 5226-5238.  
19575810 A.Chaikuad, and R.L.Brady (2009).
Conservation of structure and activity in Plasmodium purine nucleoside phosphorylases.
  BMC Struct Biol, 9, 42.
PDB codes: 3emv 3enz
19740110 G.Cacciapuoti, I.Peluso, F.Fuccio, and M.Porcelli (2009).
Purine nucleoside phosphorylases from hyperthermophilic Archaea require a CXC motif for stability and folding.
  FEBS J, 276, 5799-5805.  
19001417 P.Belenky, K.C.Christensen, F.Gazzaniga, A.A.Pletnev, and C.Brenner (2009).
Nicotinamide riboside and nicotinic acid riboside salvage in fungi and mammals. Quantitative basis for Urh1 and purine nucleoside phosphorylase function in NAD+ metabolism.
  J Biol Chem, 284, 158-164.  
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.  
17639373 A.Modrak-Wójcik, A.Kirilenko, D.Shugar, and B.Kierdaszuk (2008).
Role of ionization of the phosphate cosubstrate on phosphorolysis by purine nucleoside phosphorylase (PNP) of bacterial (E. coli) and mammalian (human) origin.
  Eur Biophys J, 37, 153-164.  
17419725 G.Cacciapuoti, S.Gorassini, M.F.Mazzeo, R.A.Siciliano, V.Carbone, V.Zappia, and M.Porcelli (2007).
Biochemical and structural characterization of mammalian-like purine nucleoside phosphorylase from the Archaeon Pyrococcus furiosus.
  FEBS J, 274, 2482-2495.  
16551572 J.E.Kim, and M.H.Chung (2006).
8-Oxo-7,8-dihydro-2'-deoxyguanosine is not salvaged for DNA synthesis in human leukemic U937 cells.
  Free Radic Res, 40, 461-466.  
16239721 A.V.Toms, W.Wang, Y.Li, B.Ganem, and S.E.Ealick (2005).
Novel multisubstrate inhibitors of mammalian purine nucleoside phosphorylase.
  Acta Crystallogr D Biol Crystallogr, 61, 1449-1458.
PDB codes: 2ai1 2ai2 2ai3
15819883 G.Cacciapuoti, S.Forte, M.A.Moretti, A.Brio, V.Zappia, and M.Porcelli (2005).
A novel hyperthermostable 5'-deoxy-5'-methylthioadenosine phosphorylase from the archaeon Sulfolobus solfataricus.
  FEBS J, 272, 1886-1899.  
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
15606771 G.Cacciapuoti, M.A.Moretti, S.Forte, A.Brio, L.Camardella, V.Zappia, and M.Porcelli (2004).
Methylthioadenosine phosphorylase from the archaeon Pyrococcus furiosus. Mechanism of the reaction and assignment of disulfide bonds.
  Eur J Biochem, 271, 4834-4844.  
15272165 M.Luić, G.Koellner, T.Yokomatsu, S.Shibuya, and A.Bzowska (2004).
Calf spleen purine-nucleoside phosphorylase: crystal structure of the binary complex with a potent multisubstrate analogue inhibitor.
  Acta Crystallogr D Biol Crystallogr, 60, 1417-1424.
PDB code: 1v48
12842889 A.Lewandowicz, P.C.Tyler, G.B.Evans, R.H.Furneaux, and V.L.Schramm (2003).
Achieving the ultimate physiological goal in transition state analogue inhibitors for purine nucleoside phosphorylase.
  J Biol Chem, 278, 31465-31468.  
12937174 E.M.Bennett, C.Li, P.W.Allan, W.B.Parker, and S.E.Ealick (2003).
Structural basis for substrate specificity of Escherichia coli purine nucleoside phosphorylase.
  J Biol Chem, 278, 47110-47118.
PDB codes: 1pk7 1pk9 1pke 1pr0 1pr1 1pr2 1pr4 1pr5 1pr6 1pw7
12180982 G.Stoychev, B.Kierdaszuk, and D.Shugar (2002).
Xanthosine and xanthine. Substrate properties with purine nucleoside phosphorylases, and relevance to other enzyme systems.
  Eur J Biochem, 269, 4048-4057.  
11201210 A.D.Andricopulo, and R.A.Yunes (2001).
Structure-activity relationships for a collection of structurally diverse inhibitors of purine nucleoside phosphorylase.
  Chem Pharm Bull (Tokyo), 49, 10-17.  
11170405 A.Fedorov, W.Shi, G.Kicska, E.Fedorov, P.C.Tyler, R.H.Furneaux, J.C.Hanson, G.J.Gainsford, J.Z.Larese, V.L.Schramm, and S.C.Almo (2001).
Transition state structure of purine nucleoside phosphorylase and principles of atomic motion in enzymatic catalysis.
  Biochemistry, 40, 853-860.
PDB code: 1b8o
11466296 K.Lecoq, I.Belloc, C.Desgranges, M.Konrad, and B.Daignan-Fornier (2001).
YLR209c encodes Saccharomyces cerevisiae purine nucleoside phosphorylase.
  J Bacteriol, 183, 4910-4913.  
11134924 M.Luić, G.Koellner, D.Shugar, W.Saenger, and A.Bzowska (2001).
Calf spleen purine nucleoside phosphorylase: structure of its ternary complex with an N(7)-acycloguanosine inhibitor and a phosphate anion.
  Acta Crystallogr D Biol Crystallogr, 57, 30-36.
PDB code: 1fxu
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
11337031 A.Bzowska, E.Kulikowska, and D.Shugar (2000).
Purine nucleoside phosphorylases: properties, functions, and clinical aspects.
  Pharmacol Ther, 88, 349-425.  
11045613 F.Wang, R.W.Miles, G.Kicska, E.Nieves, V.L.Schramm, and R.H.Angeletti (2000).
Immucillin-H binding to purine nucleoside phosphorylase reduces dynamic solvent exchange.
  Protein Sci, 9, 1660-1668.  
9817849 M.J.Pugmire, and S.E.Ealick (1998).
The crystal structure of pyrimidine nucleoside phosphorylase in a closed conformation.
  Structure, 6, 1467-1479.
PDB code: 1brw
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 code is shown on the right.