The inhibition of proinsulin-processing endopeptidase activities by active-site-directed peptides.
Inhibitor studies were performed on the two endopeptidase activities involved in proinsulin conversion in isolated insulin secretory granules [Davidson, Rhodes & Hutton (1988) Nature (London) 333, 93-96]. The active-site-directed peptides L-alanyl-L-arginyl-L-arginylmethyldimethylsulphonium and L-alanyl-L-lysyl-L-arginylmethyldimethylsulphonium inhibited these activities in accordance with the observed cleavage pattern, suggesting that the primary amino acid sequence of the dibasic site was an important determinant of the endopeptidase substrate specificities.
Rhodes
C J
CJ
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, U.K.
Zumbrunn
A
A
Bailyes
E M
EM
Shaw
E
E
Hutton
J C
JC
D000818:Animals; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D010450:Endopeptidases; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D011384:Proinsulin / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D013452:Sulfonium Compounds / Q000494:pharmacology
D009842:Oligopeptides; D010455:Peptides; D011480:Protease Inhibitors; D013452:Sulfonium Compounds; C058959:alanyl-arginyl-arginylmethyldimethylsulfonium; C058958:alanyl-lysyl-arginylmethyldimethylsulfonium; D011384:Proinsulin; D010450:Endopeptidases; C054196:proinsulin endopeptidase I; C061496:proinsulin endopeptidase II