1pr5: Difference between revisions

Revision as of 05:23, 3 May 2008

Escherichia coli Purine Nucleoside Phosphorylase Complexed with 7-deazaadenosine and Phosphate/Sulfate

OverviewOverview

Purine nucleoside phosphorylase catalyzes reversible phosphorolysis of purine nucleosides and 2'-deoxypurine nucleosides to the free base and ribose (or 2'-deoxyribose) 1-phosphate. Whereas the human enzyme is specific for 6-oxopurine ribonucleosides, the Escherichia coli enzyme accepts additional substrates including 6-oxopurine ribonucleosides, 6-aminopurine ribonucleosides, and to a lesser extent purine arabinosides. These differences have been exploited in a potential suicide gene therapy treatment for solid tumors. In an effort to optimize this suicide gene therapy approach, we have determined the three-dimensional structure of the E. coli enzyme in complex with 10 nucleoside analogs and correlated the structures with kinetic measurements and computer modeling. These studies explain the preference of the enzyme for ribose sugars, show increased flexibility for active site residues Asp204 and Arg24, and suggest that interactions involving the 1- and 6-positions of the purine and the 4'- and 5'-positions of the ribose provide the best opportunities to increase prodrug specificity and enzyme efficiency.

About this StructureAbout this Structure

1PR5 is a Single protein structure of sequence from Escherichia coli, and escherichia coli o157:h7. Full crystallographic information is available from OCA.

ReferenceReference

Structural basis for substrate specificity of Escherichia coli purine nucleoside phosphorylase., Bennett EM, Li C, Allan PW, Parker WB, Ealick SE, J Biol Chem. 2003 Nov 21;278(47):47110-8. Epub 2003 Aug 21. PMID:12937174 Page seeded by OCA on Sat May 3 05:23:53 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:1pr5.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 1pr5 |SIZE=350|CAPTION= <scene name='initialview01'>1pr5</scene>, resolution 2.5&Aring;
+The line below this paragraph, containing "STRUCTURE_1pr5", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=TBN:&#39;2-(4-AMINO-PYRROLO[2,3-D]PYRIMIDIN-7-YL)-5-HYDROXYMETHYL-TETRAHYDRO-FURAN-3,4-DIOL'>TBN</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Purine-nucleoside_phosphorylase Purine-nucleoside phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.1 2.4.2.1] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1pr5|  PDB=1pr5  |  SCENE=  }}
-|RELATEDENTRY=[[1ecp|1ECP]], [[1k9s|1K9S]], [[1pk7|1PK7]], [[1pr0|1PR0]], [[1pr1|1PR1]], [[1pr2|1PR2]], [[1pr4|1PR4]], [[1pr6|1PR6]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1pr5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pr5 OCA], [http://www.ebi.ac.uk/pdbsum/1pr5 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1pr5 RCSB]</span>
-}}
 '''Escherichia coli Purine Nucleoside Phosphorylase Complexed with 7-deazaadenosine and Phosphate/Sulfate'''
@@ Line 31: / Line 28: @@
 [[Category: Li, C.]]
 [[Category: Parker, W B.]]
-[[Category: protein-nucleoside complex]]
+[[Category: Protein-nucleoside complex]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 05:23:53 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:03:31 2008''