Steve Ealick's Research Group


Human Purine Nucleoside Phosphorylase


PDB files:

1ULA (native)

1ULB (complexed with guanine)

Description:

Human purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of ribonucleosides and 2′- deoxyribonucleosides to the free base and (2′-deoxy)ribose-1-phosphate. We have refined the crystal structure at 2.75 Å.

The most prominent feature of the PNP monomer is the distorted β-barrel made of an eight-stranded mixed β-sheet and a five-stranded mixed β-sheet joined at the edges, where four of the five strands of the smaller sheet are extensions of the larger sheet.

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The active form of human PNP is a trimer with a molecular weight of about 100 kDa. Phe159 from the neighboring monomer completes the hydrophobic environment of the bound purine base.

 

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The active site of human PNP is shown in the following schematic diagram, with residues labeled for binding the purine base and the sugar. The phosphate-binding site is similarly shown in this diagram.

References:

Narayana SVL, Bugg CE and Ealick SE. Refined Structure of Purine Nucleoside Phosphorylase at 2.75 Å Resolution. Acta Crystallogr. D 53:131-142 (1997)

Ealick SE, Rule SA, Carter DC, Greenhough TJ, Babu YS, Cook WJ, Habash J, Helliwell JR, Stoeckler JD, Parks RE Jr., Chen S-F, and Bugg CE. Three-Dimensional Structure of Human Erythrocytic Purine Nucleoside Phosphorylase at 3.2Å Resolution. J. Biol. Chem. 265:1812-1820 (1990).

Ealick SE, Greenhough TJ, Babu YS, Cook WJ, Bugg CE, Rule S, Habash G, and Helliwell J. The Crystal Structure of a Human Erythrocytic Purine Nucleoside Phosphorylase at 6Å Resolution. Acta Crystallogr. A 40:C30 (1984).

Cook WJ, Ealick SE, Bugg CE, Stoeckler JD, and Parks RE, Jr. Crystallization and Preliminary X-ray Investigation of Human Erythrocytic Purine Nucleoside Phosphorylase. J. Biol. Chem. 256(8):4079-4080 (1981).



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