Novel inhibitor cystine knot peptides from momordica charantia

He, Wen-Jun, Chan, Lai Yue, Clark, Richard J., Tang, Jun, Zeng, Guang-Zhi, Franco, Octavio L., Cantacessi, Cinzia, Craik, David J., Daly, Norelle L. and Tan, Ning-Hua (2013) Novel inhibitor cystine knot peptides from momordica charantia. PLoS ONE, 8 10: e75334.1-e75334.10. doi:10.1371/journal.pone.0075334


Author He, Wen-Jun
Chan, Lai Yue
Clark, Richard J.
Tang, Jun
Zeng, Guang-Zhi
Franco, Octavio L.
Cantacessi, Cinzia
Craik, David J.
Daly, Norelle L.
Tan, Ning-Hua
Title Novel inhibitor cystine knot peptides from momordica charantia
Journal name PLoS ONE   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-10-01
Sub-type Article (original research)
DOI 10.1371/journal.pone.0075334
Open Access Status DOI
Volume 8
Issue 10
Start page e75334.1
End page e75334.10
Total pages 11
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Language eng
Formatted abstract
Two new peptides, MCh-1 and MCh-2, along with three known trypsin inhibitors (MCTI-I, MCTI-II and MCTI-III), were isolated from the seeds of the tropical vine Momordica charantia. The sequences of the peptides were determined using mass spectrometry and NMR spectroscopy. Using a strategy involving partial reduction and stepwise alkylation of the peptides, followed by enzymatic digestion and tandem mass spectrometry sequencing, the disulfide connectivity of MCh-1 was elucidated to be CysI-CysIV, CysII-CysV and CysIII-CysVI. The three-dimensional structures of MCh-1 and MCh-2 were determined using NMR spectroscopy and found to contain the inhibitor cystine knot (ICK) motif. The sequences of the novel peptides differ significantly from peptides previously isolated from this plant. Therefore, this study expands the known peptide diversity in M. charantia and the range of sequences that can be accommodated by the ICK motif. Furthermore, we show that a stable two-disulfide intermediate is involved in the oxidative folding of MCh-1. This disulfide intermediate is structurally homologous to the proposed ancestral fold of ICK peptides, and provides a possible pathway for the evolution of this structural motif, which is highly prevalent in nature.
Keyword Amino Acid Sequences
Trypsin Inhibitor
Plasmodium falciparum
Proteinase Inhibitors
Cytotoxic Cyclotides
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Biomedical Sciences Publications
Institute for Molecular Bioscience - Publications
 
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