Role of beta-turn in proteolytic processing of peptide hormone precursors at dibasic sites

Details

Serval ID
serval:BIB_AF4D1D69EF8E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Role of beta-turn in proteolytic processing of peptide hormone precursors at dibasic sites
Journal
Biochemistry
Author(s)
Brakch  N., Rholam  M., Boussetta  H., Cohen  P.
ISSN
0006-2960 (Print)
Publication state
Published
Issued date
05/1993
Volume
32
Number
18
Pages
4925-30
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May 11
Abstract
Proteolytic activation of prohormones and proproteins occurs most frequently at the level of basic amino acids arranged in doublets. Previous predictions by Rholam et al. [Rholam, M., Nicolas, P., & Cohen, P. (1986) FEBS Lett. 207. 1-6] have indicated, on the basis of 20 prohormone sequences containing 53 dibasic potential processing sites, that dibasic sites situated in, or next to, beta-turns were cleaved in vivo, whereas sites included in ordered structures like beta-sheets or alpha-helices were not. We have used peptide analogs of the proocytocin/neurophysin processing domain and a purified preparation of the putative proocytocin convertase from bovine tissues as a model to demonstrate that (1) processing at dibasic sites is associated with a prohormone sequence organized in a beta-turn structure; (2) the beta-turn is an interchangeable motif since the original sequence could be replaced by an heterologous one possessing the ability to organize as a beta-turn; and (3) this particular secondary structure participates in the catalytic reaction, most likely by favoring the interactions of the substrate with the processing endoprotease. It is concluded that, in addition to the dibasic and other amino acids around the cleavage loci, the beta-turn constitutes a key feature in the proteolytic processing reaction in participating as the favorable conformation for optimal substrate-enzyme active site recognition.
Keywords
Amino Acid Sequence Circular Dichroism Endopeptidases/*metabolism Hormones/metabolism Molecular Sequence Data Protein Precursors/*metabolism *Protein Processing, Post-Translational Protein Sorting Signals/*metabolism *Protein Structure, Secondary Structure-Activity Relationship Substrate Specificity
Pubmed
Web of science
Create date
28/01/2008 10:35
Last modification date
20/08/2019 15:18
Usage data