Ligand effects on the limited proteolysis of phenylalanine hydroxylase: evidence for multiple conformational states.
The effects of phenylalanine and tetrahydrobiopterin on the limited proteolysis of rat liver phenylalanine hydroxylase by chymotrypsin have been examined. The presence of tetrahydrobiopterin inhibits the proteolytic activation of native phenylalanine hydroxylase. In contrast, phenylalanine causes a stimulation of proteolytic activation under these conditions. Neither phenylalanine nor tetrahydrobiopterin affect the rate of hydrolysis of a synthetic substrate by chymotrypsin. Both tetrahydrobiopterin and phenylalanine inhibit the release of soluble radioactivity from [32P]phosphorylated phenylalanine hydroxylase. These results confirm the existence of multiple conformational states of phenylalanine hydroxylase.
D000818:Animals; D001665:Binding Sites; D001708:Biopterins / Q000031:analogs & derivatives / Q000494:pharmacology; D002918:Chymotrypsin / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D011919:Rats, Inbred Strains
D001708:Biopterins; D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase; D002918:Chymotrypsin; C003402:sapropterin