1pr6
From Proteopedia
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'''Escherichia coli Purine Nucleoside Phosphorylase Complexed with 9-beta-D-xylofuranosyladenine and Phosphate/Sulfate''' | '''Escherichia coli Purine Nucleoside Phosphorylase Complexed with 9-beta-D-xylofuranosyladenine and Phosphate/Sulfate''' | ||
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[[Category: Li, C.]] | [[Category: Li, C.]] | ||
[[Category: Parker, W B.]] | [[Category: Parker, W B.]] | ||
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Revision as of 02:23, 3 May 2008
Escherichia coli Purine Nucleoside Phosphorylase Complexed with 9-beta-D-xylofuranosyladenine and Phosphate/Sulfate
Overview
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 Structure
1PR6 is a Single protein structure of sequence from Escherichia coli, and escherichia coli o157:h7. Full crystallographic information is available from OCA.
Reference
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 05:23:55 2008
