In vitro and ex vivo inhibition of hepatitis A virus 3C proteinase by a peptidyl monofluoromethyl ketone.

Hepatitis A virus (HAV) 3C proteinase is the enzyme responsible for the processing of the viral polyprotein. Although a cysteine proteinase, it displays an active site configuration like those of the mammalian serine proteinases (Malcolm, B. A.

Peptide aldehyde inhibitors of hepatitis A virus 3C proteinase.

Picornaviral 3C proteinases are a group of closely related thiol proteinases responsible for processing of the viral polyprotein into its component proteins. These proteinases adopt a chymotrypsin-like fold [Allaire et al. (1994) Nature 369, 72-77; Matthews et al.

Site-site interactions in glycogen phosphorylase b probed by ligands specific for each site.

Three ligand binding sites on glycogen phosphorylase b which were originally described by kinetic and physicochemical means, and more recently located and defined in molecular terms by X-ray crystallography, have been probed by ligands specific for each site. Kinetic analyses, supplemented by X-ray crystallographic binding studies, permit assignment of each ligand to a primary binding site, as well as determination of its dissociation constant and interaction with ligands binding to the other sites. 8-Anilino-1-naphthalenesulfonate binds most strongly to the activator site, in competition with adenosine 5'-phosphate, presumably because its sulfonate group interacts with several arginine residues, and binds only weakly to the hydrophobic inhibitor site, possibly because of charge repulsion.

Synergistic regulation of phosphorylase a by glucose and caffeine.

Kinetic studies of both liver and muscle phosphorylase a demonstrate that caffeine and glucose inhibit the binding of glucose 1-phosphate to the enzyme in a synergistic competitive and nonexclusive manner. Inhibition studies for numerous other caffeine analogs show that the muscle enzyme has a relaxed specificity for this negative effector. The liver enzyme is more discriminating by preferential binding of methylated oxypurines.