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). pp. 1-11.

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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.

Item ID: 30190
Item Type: Article (Refereed Research - C1)
Additional Information:

© 2013 He et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ISSN: 1932-6203
Funders: National Basic Research Program of China, National New Drug Innovation Great Project of China, National Natural Science Foundation of China, Chinese Academy of Sciences, Natural Science Foundation of Yunnan Province, Australian Research Council (ARC), National Health and Medical Research Council (NHMRC), Conselho Nacional de Desenvolvimento Científico e Tecnológico, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Fundação de Apoio a Pesquisa do Distrito Federal
Projects and Grants: National Basic Research Program of China 2013CB127505, National Basic Research Program of China 2009CB522300, National New Drug Innovation Great Project of China 2011ZX09307-002-02, National Natural Science Foundation of China 21202174, National Natural Science Foundation of China U1032602, National Natural Science Foundation of China 91013002, National Natural Science Foundation of China 30725048, Natural Science Foundation of Yunnan Province 2012GA003
Date Deposited: 13 Nov 2013 05:27
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110106 Medical Biochemistry: Proteins and Peptides (incl Medical Proteomics) @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 100%
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