Steve Ealick's Research Group
Human Purine Nucleoside Phosphorylase
1ULB (complexed with guanine)
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.|
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.
Click the image to enlarge.
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.
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).