Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Discovery of a Beetroot Protease Inhibitor to Identify and Classify Plant-Derived Cystine Knot Peptides

Full text
Author(s):
Retzl, Bernhard [1] ; Hellinger, Roland [1] ; Muratspahic, Edin [1] ; Pinto, Meri E. F. [1, 2] ; Bolzani, Vanderlan S. [2] ; Gruber, Christian W. [1]
Total Authors: 6
Affiliation:
[1] Med Univ Vienna, Ctr Physiol & Pharmacol, A-1090 Vienna - Austria
[2] Sao Paulo State Univ UNESP, Inst Chem, BR-14800060 Araraquara, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Journal of Natural Products; v. 83, n. 11, p. 3305-3314, NOV 25 2020.
Web of Science Citations: 4
Abstract

Plant peptide protease inhibitors are important molecules in seed storage metabolism and to fight insect pests. Commonly they contain multiple disulfide bonds and are exceptionally stable molecules. In this study, a novel peptide protease inhibitor from beetroot (Beta vulgaris) termed bevuTI-I was isolated, and its primary structure was determined via mass spectrometry-based amino acid sequencing. By sequence homology analysis a few peptides with high similarity to bevuTI-I, also known as the Mirabilis jalapa trypsin inhibitor subfamily of knottin-type protease inhibitors, were discovered. Hence, we assessed bevuTI-I for inhibitory activity toward trypsin (IC50 = 471 nM) and human prolyl oligopeptidase (IC50 = 11 mu M), which is an emerging drug target for neurodegenerative and inflammatory disorders. Interestingly, using a customized bioinformatics approach, bevuTI-I was found to be the missing link to annotate 243 novel sequences of M. jalapa trypsin inhibitor-like peptides. According to their phylogenetic distribution they appear to be common in several plant families. Therefore, the presented approach and our results may help to discover and classify other plant-derived cystine knot peptides, a class of plant molecules that play important functions in plant physiology and are currently being explored as lead molecules and scaffolds in drug development. (AU)

FAPESP's process: 19/04381-5 - The Last Advances on Solid-Phase Peptide Synthesis and NMR New Methodologies Applied to Cyclotides from Brazilian Plant Species
Grantee:Meri Emili Pinto Nascimento
Support Opportunities: Scholarships abroad - Research Internship - Post-doctor