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Structural insights and molecular dynamics into the inhibitory mechanism of a Kunitz-type trypsin inhibitor from Tamarindus indica L
Trypsin inhibitors from tamarind seed have been studied in vitro and in preclinical studies for the treatment of obesity, its complications and associated comorbidities. It is still necessary to fully understand the structure and behaviour of these molecules. We purifed this inhibitor, sequenced de...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Taylor & Francis
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875565/ https://www.ncbi.nlm.nih.gov/pubmed/33491503 http://dx.doi.org/10.1080/14756366.2021.1876686 |
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author | de Medeiros, Amanda Fernandes de Souza, Beatriz Blenda Pinheiro Coutinho, Lucas Pinheiro Murad, Aline Melro dos Santos, Paula Ivani Medeiros Monteiro, Norberto de Kássio Vieira dos Santos, Elizeu Antunes Maciel, Bruna Leal Lima de Araújo Morais, Ana Heloneida |
author_facet | de Medeiros, Amanda Fernandes de Souza, Beatriz Blenda Pinheiro Coutinho, Lucas Pinheiro Murad, Aline Melro dos Santos, Paula Ivani Medeiros Monteiro, Norberto de Kássio Vieira dos Santos, Elizeu Antunes Maciel, Bruna Leal Lima de Araújo Morais, Ana Heloneida |
author_sort | de Medeiros, Amanda Fernandes |
collection | PubMed |
description | Trypsin inhibitors from tamarind seed have been studied in vitro and in preclinical studies for the treatment of obesity, its complications and associated comorbidities. It is still necessary to fully understand the structure and behaviour of these molecules. We purifed this inhibitor, sequenced de novo by MALDI-TOF/TOF, performed its homology modelling, and assessed the interaction with the trypsin enzyme through molecular dynamics (MD) simulation under physiological conditions. We identified additional 75 amino acid residues, reaching approximately 72% of total coverage. The four best conformations of the best homology modelling were submitted to the MD. The conformation n°287 was selected considering the RMSD analysis and interaction energy (–301.0128 kcal.mol(−1)). Residues Ile (54), Pro (57), Arg (59), Arg (63), and Glu (78) of pTTI presented the highest interactions with trypsin, and arginine residues were mainly involved in its binding mechanism. The results favour bioprospecting of this protein for pharmaceutical health applications. |
format | Online Article Text |
id | pubmed-7875565 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-78755652021-03-05 Structural insights and molecular dynamics into the inhibitory mechanism of a Kunitz-type trypsin inhibitor from Tamarindus indica L de Medeiros, Amanda Fernandes de Souza, Beatriz Blenda Pinheiro Coutinho, Lucas Pinheiro Murad, Aline Melro dos Santos, Paula Ivani Medeiros Monteiro, Norberto de Kássio Vieira dos Santos, Elizeu Antunes Maciel, Bruna Leal Lima de Araújo Morais, Ana Heloneida J Enzyme Inhib Med Chem Research Paper Trypsin inhibitors from tamarind seed have been studied in vitro and in preclinical studies for the treatment of obesity, its complications and associated comorbidities. It is still necessary to fully understand the structure and behaviour of these molecules. We purifed this inhibitor, sequenced de novo by MALDI-TOF/TOF, performed its homology modelling, and assessed the interaction with the trypsin enzyme through molecular dynamics (MD) simulation under physiological conditions. We identified additional 75 amino acid residues, reaching approximately 72% of total coverage. The four best conformations of the best homology modelling were submitted to the MD. The conformation n°287 was selected considering the RMSD analysis and interaction energy (–301.0128 kcal.mol(−1)). Residues Ile (54), Pro (57), Arg (59), Arg (63), and Glu (78) of pTTI presented the highest interactions with trypsin, and arginine residues were mainly involved in its binding mechanism. The results favour bioprospecting of this protein for pharmaceutical health applications. Taylor & Francis 2021-01-24 /pmc/articles/PMC7875565/ /pubmed/33491503 http://dx.doi.org/10.1080/14756366.2021.1876686 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper de Medeiros, Amanda Fernandes de Souza, Beatriz Blenda Pinheiro Coutinho, Lucas Pinheiro Murad, Aline Melro dos Santos, Paula Ivani Medeiros Monteiro, Norberto de Kássio Vieira dos Santos, Elizeu Antunes Maciel, Bruna Leal Lima de Araújo Morais, Ana Heloneida Structural insights and molecular dynamics into the inhibitory mechanism of a Kunitz-type trypsin inhibitor from Tamarindus indica L |
title | Structural insights and molecular dynamics into the inhibitory mechanism of a Kunitz-type trypsin inhibitor from Tamarindus indica L |
title_full | Structural insights and molecular dynamics into the inhibitory mechanism of a Kunitz-type trypsin inhibitor from Tamarindus indica L |
title_fullStr | Structural insights and molecular dynamics into the inhibitory mechanism of a Kunitz-type trypsin inhibitor from Tamarindus indica L |
title_full_unstemmed | Structural insights and molecular dynamics into the inhibitory mechanism of a Kunitz-type trypsin inhibitor from Tamarindus indica L |
title_short | Structural insights and molecular dynamics into the inhibitory mechanism of a Kunitz-type trypsin inhibitor from Tamarindus indica L |
title_sort | structural insights and molecular dynamics into the inhibitory mechanism of a kunitz-type trypsin inhibitor from tamarindus indica l |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875565/ https://www.ncbi.nlm.nih.gov/pubmed/33491503 http://dx.doi.org/10.1080/14756366.2021.1876686 |
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