1PK9: Crystal Structure Of E. Coli Purine Nucleoside Phosphorylase Complexed With 2-fluoroadenosine And Sulfate/phosphate

Citation:
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.
PDB ID: 1PK9Download
MMDB ID: 25343
PDB Deposition Date: 2003/6/5
Updated in MMDB: 2003/12
Experimental Method:
x-ray diffraction
Resolution: 1.9  Å
Source Organism:
Similar Structures:
Biological Unit for 1PK9: hexameric; determined by author and by software (PISA,PQS)
Molecular Components in 1PK9
Label Count Molecule
Proteins (6 molecules)
6
Purine Nucleoside Phosphorylase
Molecule annotation
Chemicals (12 molecules)
1
6
2
6
* Click molecule labels to explore molecular sequence information.

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