Discovery of a Beetroot Protease Inhibitor to Identify and Classify Plant-Derived Cystine Knot Peptides
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1021/acs.jnatprod.0c00648 http://hdl.handle.net/11449/208130 |
Resumo: | 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 μM), 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. |
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Discovery of a Beetroot Protease Inhibitor to Identify and Classify Plant-Derived Cystine Knot PeptidesPlant 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 μM), 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.Center for Physiology and Pharmacology Medical University of Vienna, Schwarzspanierstraße 17Institute of Chemistry São Paulo State University-UNESPInstitute of Chemistry São Paulo State University-UNESPMedical University of ViennaUniversidade Estadual Paulista (Unesp)Retzl, BernhardHellinger, RolandMuratspahić, EdinPinto, Meri E. F. [UNESP]Bolzani, Vanderlan S. [UNESP]Gruber, Christian W.2021-06-25T11:06:53Z2021-06-25T11:06:53Z2020-11-25info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article3305-3314http://dx.doi.org/10.1021/acs.jnatprod.0c00648Journal of Natural Products, v. 83, n. 11, p. 3305-3314, 2020.1520-60250163-3864http://hdl.handle.net/11449/20813010.1021/acs.jnatprod.0c006482-s2.0-85095852642Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Natural Productsinfo:eu-repo/semantics/openAccess2021-10-23T18:56:44Zoai:repositorio.unesp.br:11449/208130Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-23T18:56:44Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Discovery of a Beetroot Protease Inhibitor to Identify and Classify Plant-Derived Cystine Knot Peptides |
title |
Discovery of a Beetroot Protease Inhibitor to Identify and Classify Plant-Derived Cystine Knot Peptides |
spellingShingle |
Discovery of a Beetroot Protease Inhibitor to Identify and Classify Plant-Derived Cystine Knot Peptides Retzl, Bernhard |
title_short |
Discovery of a Beetroot Protease Inhibitor to Identify and Classify Plant-Derived Cystine Knot Peptides |
title_full |
Discovery of a Beetroot Protease Inhibitor to Identify and Classify Plant-Derived Cystine Knot Peptides |
title_fullStr |
Discovery of a Beetroot Protease Inhibitor to Identify and Classify Plant-Derived Cystine Knot Peptides |
title_full_unstemmed |
Discovery of a Beetroot Protease Inhibitor to Identify and Classify Plant-Derived Cystine Knot Peptides |
title_sort |
Discovery of a Beetroot Protease Inhibitor to Identify and Classify Plant-Derived Cystine Knot Peptides |
author |
Retzl, Bernhard |
author_facet |
Retzl, Bernhard Hellinger, Roland Muratspahić, Edin Pinto, Meri E. F. [UNESP] Bolzani, Vanderlan S. [UNESP] Gruber, Christian W. |
author_role |
author |
author2 |
Hellinger, Roland Muratspahić, Edin Pinto, Meri E. F. [UNESP] Bolzani, Vanderlan S. [UNESP] Gruber, Christian W. |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Medical University of Vienna Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Retzl, Bernhard Hellinger, Roland Muratspahić, Edin Pinto, Meri E. F. [UNESP] Bolzani, Vanderlan S. [UNESP] Gruber, Christian W. |
description |
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 μM), 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. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-11-25 2021-06-25T11:06:53Z 2021-06-25T11:06:53Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1021/acs.jnatprod.0c00648 Journal of Natural Products, v. 83, n. 11, p. 3305-3314, 2020. 1520-6025 0163-3864 http://hdl.handle.net/11449/208130 10.1021/acs.jnatprod.0c00648 2-s2.0-85095852642 |
url |
http://dx.doi.org/10.1021/acs.jnatprod.0c00648 http://hdl.handle.net/11449/208130 |
identifier_str_mv |
Journal of Natural Products, v. 83, n. 11, p. 3305-3314, 2020. 1520-6025 0163-3864 10.1021/acs.jnatprod.0c00648 2-s2.0-85095852642 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal of Natural Products |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
3305-3314 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1799965362509316096 |