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PDBsum entry 1ulb

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Pentosyltransferase PDB id
1ulb
Jmol
Contents
Protein chain
289 a.a. *
Ligands
SO4 ×2
GUN
* Residue conservation analysis
PDB id:
1ulb
Name: Pentosyltransferase
Title: Application of crystallographic and modeling methods in the purine nucleoside phosphorylase inhibitors
Structure: Purine nucleoside phosphorylase. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
Biol. unit: Trimer (from PQS)
Resolution:
2.75Å     R-factor:   0.204    
Authors: S.E.Ealick,S.A.Rule,D.C.Carter,T.J.Greenhough,Y.S.Babu,W.J.C J.Habash,J.R.Helliwell,J.D.Stoeckler,R.E.Parksjunior,S.-F.C C.E.Bugg
Key ref: S.E.Ealick et al. (1991). Application of crystallographic and modeling methods in the design of purine nucleoside phosphorylase inhibitors. Proc Natl Acad Sci U S A, 88, 11540-11544. PubMed id: 1763067 DOI: 10.1073/pnas.88.24.11540
Date:
05-Nov-91     Release date:   15-Jan-93    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00491  (PNPH_HUMAN) -  Purine nucleoside phosphorylase
Seq:
Struc:
289 a.a.
289 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 = GUN)
matches with 81.82% similarity
+ 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  

 

 
    reference    
 
 
DOI no: 10.1073/pnas.88.24.11540 Proc Natl Acad Sci U S A 88:11540-11544 (1991)
PubMed id: 1763067  
 
 
Application of crystallographic and modeling methods in the design of purine nucleoside phosphorylase inhibitors.
S.E.Ealick, Y.S.Babu, C.E.Bugg, M.D.Erion, W.C.Guida, J.A.Montgomery, J.A.Secrist.
 
  ABSTRACT  
 
Competitive inhibitors of the salvage pathway enzyme purine-nucleoside phosphorylase (purine-nucleoside:orthophosphate ribosyltransferase, EC 2.4.2.1) have been designed by using the three-dimensional structure of the enzyme as determined by x-ray crystallography. The process was an iterative one that utilized interactive computer graphics, Monte Carlo-based conformational searching, energy minimization, and x-ray crystallography. The proposed compounds were synthesized and tested by an in vitro assay. Among the compounds designed and synthesized are the most potent competitive inhibitors of purine nucleoside phosphorylase thus far reported.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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
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
19191546 M.Ghanem, N.Zhadin, R.Callender, and V.L.Schramm (2009).
Loop-tryptophan human purine nucleoside phosphorylase reveals submillisecond protein dynamics.
  Biochemistry, 48, 3658-3668.  
  20150996 Z.Bikadi, and E.Hazai (2009).
Application of the PM6 semi-empirical method to modeling proteins enhances docking accuracy of AutoDock.
  J Cheminform, 1, 15.  
18234834 S.Saen-Oon, M.Ghanem, V.L.Schramm, and S.D.Schwartz (2008).
Remote mutations and active site dynamics correlate with catalytic properties of purine nucleoside phosphorylase.
  Biophys J, 94, 4078-4088.  
  20664707 S.Saen-Oon, V.L.Schramm, and S.D.Schwartz (2008).
Transition Path Sampling Study of the Reaction Catalyzed by Purine Nucleoside Phosphorylase.
  Z Phys Chem (N F), 222, 1359-1374.  
15916423 A.P.Graves, R.Brenk, and B.K.Shoichet (2005).
Decoys for docking.
  J Med Chem, 48, 3714-3728.
PDB code: 1xep
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
15983407 F.Canduri, R.G.Silva, D.M.dos Santos, M.S.Palma, L.A.Basso, D.S.Santos, and W.F.de Azevedo (2005).
Structure of human PNP complexed with ligands.
  Acta Crystallogr D Biol Crystallogr, 61, 856-862.
PDB codes: 1rfg 1v41 1v45
15538770 K.Lee, C.Czaplewski, S.Y.Kim, and J.Lee (2005).
An efficient molecular docking using conformational space annealing.
  J Comput Chem, 26, 78-87.  
15047506 A.S.Ray, L.Olson, and A.Fridland (2004).
Role of purine nucleoside phosphorylase in interactions between 2',3'-dideoxyinosine and allopurinol, ganciclovir, or tenofovir.
  Antimicrob Agents Chemother, 48, 1089-1095.  
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
14671495 J.C.Bennett (2003).
Celebrating the SSCI: the drug discovery pathway: challenges and pitfalls.
  Am J Med Sci, 326, 329-332.  
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.  
11287638 G.A.Kicska, L.Long, H.Hörig, C.Fairchild, P.C.Tyler, R.H.Furneaux, V.L.Schramm, and H.L.Kaufman (2001).
Immucillin H, a powerful transition-state analog inhibitor of purine nucleoside phosphorylase, selectively inhibits human T lymphocytes.
  Proc Natl Acad Sci U S A, 98, 4593-4598.  
11337031 A.Bzowska, E.Kulikowska, and D.Shugar (2000).
Purine nucleoside phosphorylases: properties, functions, and clinical aspects.
  Pharmacol Ther, 88, 349-425.  
9585525 C.Mao, W.J.Cook, M.Zhou, A.A.Federov, S.C.Almo, and S.E.Ealick (1998).
Calf spleen purine nucleoside phosphorylase complexed with substrates and substrate analogues.
  Biochemistry, 37, 7135-7146.
PDB codes: 1a9o 1a9p 1a9q 1a9r 1a9s 1a9t 1pbn
9305963 M.D.Erion, J.D.Stoeckler, W.C.Guida, R.L.Walter, and S.E.Ealick (1997).
Purine nucleoside phosphorylase. 2. Catalytic mechanism.
  Biochemistry, 36, 11735-11748.  
9305962 M.D.Erion, K.Takabayashi, H.B.Smith, J.Kessi, S.Wagner, S.Hönger, S.L.Shames, and S.E.Ealick (1997).
Purine nucleoside phosphorylase. 1. Structure-function studies.
  Biochemistry, 36, 11725-11734.  
9667869 V.L.Schramm (1997).
Enzymatic N-riboside scission in RNA and RNA precursors.
  Curr Opin Chem Biol, 1, 323-331.  
8706713 A.Bzowska, E.Kulikowska, N.E.Poopeiko, and D.Shugar (1996).
Kinetics of phosphorolysis of 3-(beta-D-ribofuranosyl)adenine and 3-(beta-D-ribofuranosyl)hypoxanthine, non-conventional substrates of purine-nucleoside phosphorylase.
  Eur J Biochem, 239, 229-234.  
8994885 M.A.Navia (1996).
Protein-drug complexes important for immunoregulation and organ transplantation.
  Curr Opin Struct Biol, 6, 838-847.  
8785317 M.J.Sutcliffe, Z.G.Wo, and R.E.Oswald (1996).
Three-dimensional models of non-NMDA glutamate receptors.
  Biophys J, 70, 1575-1589.  
8734425 S.Freeman, and J.M.Gardiner (1996).
Acyclic nucleosides as antiviral compounds.
  Mol Biotechnol, 5, 125-137.  
8853794 Y.Wada, A.Yagihashi, K.Terasawa, N.Miyao, K.Hirata, J.Cicciarelli, and Y.Iwaki (1996).
BCX-34: a novel T-cell selective immunosuppressant: purine nucleoside phosphorylase (PNP) inhibitor.
  Artif Organs, 20, 849-852.  
  8770367 M.W.Parker (1995).
Protein crystallography in Australia.
  Aust N Z J Med, 25, 876-882.  
7744063 R.Schuster, and H.G.Holzhütter (1995).
Use of mathematical models for predicting the metabolic effect of large-scale enzyme activity alterations. Application to enzyme deficiencies of red blood cells.
  Eur J Biochem, 229, 403-418.  
8041800 H.Kubinyi (1994).
[The key and the lock. I. The basis of drug action]
  Pharm Unserer Zeit, 23, 158-168.  
7876901 S.K.Kearsley, D.J.Underwood, R.P.Sheridan, and M.D.Miller (1994).
Flexibases: a way to enhance the use of molecular docking methods.
  J Comput Aided Mol Des, 8, 565-582.  
8128192 W.H.Boehncke, R.B.Gilbertsen, J.Hemmer, and W.Sterry (1994).
Evidence for a pathway independent from 2'-deoxyguanosine and reversible by IL-2 by which purine nucleoside phosphorylase inhibitors block T-cell proliferation.
  Scand J Immunol, 39, 327-332.  
8273599 D.J.Wilburn, M.K.Dong, and R.B.Gilbertsen (1993).
PD 141955 and CI-972: 9-deazaguanine analog purine nucleoside phosphorylase inhibitors. I. Suppression of the human mixed lymphocyte reaction (MLR).
  Agents Actions, 39, C96-C98.  
8457664 K.A.McGroddy, A.A.Carter, M.M.Tubbert, and R.E.Oswald (1993).
Analysis of cyclic and acyclic nicotinic cholinergic agonists using radioligand binding, single channel recording, and nuclear magnetic resonance spectroscopy.
  Biophys J, 64, 325-338.  
8273600 M.K.Dong, and R.B.Gilbertsen (1993).
PD 141955 and CI-972: 9-deazaguanine analog purine nucleoside phosphorylase inhibitors. II. Effects on nucleoside catabolism in human and rat blood in vitro.
  Agents Actions, 39, C99-101.  
8363227 S.E.Ealick, Y.S.Babu, C.E.Bugg, M.D.Erion, W.G.Guida, J.A.Montgomery, and J.A.Secrist (1993).
Application of X-ray crystallographic methods in the design of purine nucleoside phosphorylase inhibitors.
  Ann N Y Acad Sci, 685, 237-247.  
7689377 S.W.Fesik (1993).
NMR structure-based drug design.
  J Biomol NMR, 3, 261-269.  
8103311 V.St Georgiev (1993).
Enzymes of the purine metabolism: inhibition and therapeutic potential.
  Ann N Y Acad Sci, 685, 207-216.  
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.