1PK7

Crystal Structure of E. coli purine nucleoside phosphorylase complexed with adenosine and sulfate/phosphate

Summary for 1PK7

• Entry DOI: 10.2210/pdb1pk7/pdb
• Related: 1ECP 1K9S 1ODJ 1PK9 1PKE 3PNP
• Descriptor: Purine nucleoside phosphorylase DeoD-type, PHOSPHATE ION, ADENOSINE, ... (4 entities in total)
• Functional Keywords: hexamer, protein-nucleoside complex, trimer of dimers, transferase
• Biological source: Escherichia coli O157:H7
• Total number of polymer chains: 3
• Total formula weight: 78251.54

Authors

Bennett, E.M.,Li, C.,Allan, P.W.,Parker, W.B.,Ealick, S.E. (deposition date: 2003-06-05, release date: 2003-11-25, Last modification date: 2023-08-16)

Primary citation

Bennett, E.M.,Li, C.,Allan, P.W.,Parker, W.B.,Ealick, S.E.
Structural basis for substrate specificity of Escherichia coli purine nucleoside phosphorylase.
J.Biol.Chem., 278:47110-47118, 2003

PubMed Abstract: 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.

PubMed: 12937174
DOI: 10.1074/jbc.M304622200

Experimental method

X-RAY DIFFRACTION (2.5 Å)