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PMID: 2649090 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The inhibition of proinsulin-processing endopeptidase activities by active-site-directed peptides.

The Biochemical journal ·Vol. 258 ·No. 1 ·1989-02-15 ·Pages 305-8

Rhodes CJ, Zumbrunn A, Bailyes EM, Shaw E, Hutton JC

Abstract

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.

MeSH Terms
Animals Binding Sites Dose-Response Relationship, Drug Endopeptidases Oligopeptides/pharmacology Peptides/pharmacology Proinsulin/metabolism Protease Inhibitors/pharmacology Rats Sulfonium Compounds/pharmacology
Chemicals
Oligopeptides Peptides Protease Inhibitors Sulfonium Compounds alanyl-arginyl-arginylmethyldimethylsulfonium alanyl-lysyl-arginylmethyldimethylsulfonium Proinsulin Endopeptidases proinsulin endopeptidase I proinsulin endopeptidase II
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Rhodes C J
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, U.K.
Zumbrunn A
Bailyes E M
Shaw E
Hutton J C
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj2580305
Published
1989-02-15
Pages
305-8
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1138356
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1042/bj2580305 PMC Full Text View journal details
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