PMID: 3143403Sep 6, 1988Paper

Channels at the catalytic site of glycogen phosphorylase b: binding and kinetic studies with the beta-glycosidase inhibitor D-gluconohydroximo-1,5-lactone N-phenylurethane

Biochemistry
D BarfordL N Johnson

Abstract

Regions of low packing density in the vicinity of the catalytic site of glycogen phosphorylase b are described with the aid of a computer program that generates a contour map in which the contour level is inversely proportional to the packing density in the protein. It is shown that, although there is no direct route from the catalytic site to the surface, there are two possible channels that could allow access for substrates following conformational changes in the enzyme. The first channel, channel 1, leads from the catalytic site to the surface close to the nucleoside inhibitor site and requires movements of residues 280-285 and Arg 569 in order to obtain access. Previous crystallographic experiments have shown that in the presence of substrates or R-state inhibitors these parts of the polypeptide chain undergo large conformational changes. The properties of the second channel (channel 2), which is the more extensive channel, have been investigated with the potent beta-glycosidase inhibitor D-gluconohydroximo-1,5-lactone N-phenylurethane (PUG). Crystallographic binding studies at 2.4-A resolution show that the compound binds neatly at the catalytic site of phosphorylase b. The glucopyranosylidene ring, in the half-chair confo...Continue Reading

References

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Citations

Sep 1, 1992·Protein Science : a Publication of the Protein Society·D D LeonidasT G Sotiroudis
Dec 1, 1995·Protein Science : a Publication of the Protein Society·N G OikonomakosK R Acharya
Feb 5, 1990·Journal of Molecular Biology·L N JohnsonP J McLaughlin
Sep 1, 1992·Journal of Molecular Graphics·J S Delaney
May 1, 1997·Nature Structural Biology·M O'ReillyL N Johnson
May 2, 1988·European Journal of Biochemistry·N G OikonomakosL N Johnson
Nov 25, 2004·Journal of Molecular Biology·Alison L Cuff, Andrew C R Martin
Oct 11, 2005·Bioorganic & Medicinal Chemistry·Melissa PerreiraJohn A Hanover
Aug 1, 1989·Archives of Biochemistry and Biophysics·A C PapageorgiouD D Leonidas
Jul 5, 1989·Journal of Molecular Biology·K R AcharyaD C Phillips

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