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Evaluating Molecular Mechanism of Hypotensive Peptides Interactions with Renin and Angiotensin Converting Enzyme
Our previous study showed that three rapeseed protein-derived peptides (TF, LY and RALP) inhibited the in vitro activities of angiotensin converting enzyme (ACE) and renin. Oral administration of these peptides to spontaneously hypertensive rats led to reductions in systolic blood pressure. In the p...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946342/ https://www.ncbi.nlm.nih.gov/pubmed/24603692 http://dx.doi.org/10.1371/journal.pone.0091051 |
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author | He, Rong Aluko, Rotimi E. Ju, Xing-Rong |
author_facet | He, Rong Aluko, Rotimi E. Ju, Xing-Rong |
author_sort | He, Rong |
collection | PubMed |
description | Our previous study showed that three rapeseed protein-derived peptides (TF, LY and RALP) inhibited the in vitro activities of angiotensin converting enzyme (ACE) and renin. Oral administration of these peptides to spontaneously hypertensive rats led to reductions in systolic blood pressure. In the present work, we examined the potential molecular mechanisms responsible for the ACE- and renin-inhibitory activities of these peptides. Enzyme inhibition kinetics showed competitive, non-competitive and mixed-type peptide-dependent inhibition of renin and ACE activities. Intrinsic fluorescence intensity data showed that LY and RALP have stronger binding effects on ACE molecule compared to that of TF. LY and RALP showed the highest inhibition of ACE and renin activities, respectively. Circular dichroism data showed that the inhibitory mechanism involved extensive peptide-dependent reductions in α-helix and β-sheet fractions of ACE and renin protein conformations. Molecular docking studies confirmed that the higher renin-inhibitory activity of RALP may be due to formation of several hydrogen bonds (H-bonds) with the enzyme’s active site residues. The rapeseed peptides inhibited renin and ACE activities mostly through binding to enzyme active site or non-active sites and forming extensive H-bonds that distorted the normal configuration required for catalysis. Data presented from this work could enhance development of highly potent antihypertensive natural peptides or peptidomimetics. |
format | Online Article Text |
id | pubmed-3946342 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39463422014-03-12 Evaluating Molecular Mechanism of Hypotensive Peptides Interactions with Renin and Angiotensin Converting Enzyme He, Rong Aluko, Rotimi E. Ju, Xing-Rong PLoS One Research Article Our previous study showed that three rapeseed protein-derived peptides (TF, LY and RALP) inhibited the in vitro activities of angiotensin converting enzyme (ACE) and renin. Oral administration of these peptides to spontaneously hypertensive rats led to reductions in systolic blood pressure. In the present work, we examined the potential molecular mechanisms responsible for the ACE- and renin-inhibitory activities of these peptides. Enzyme inhibition kinetics showed competitive, non-competitive and mixed-type peptide-dependent inhibition of renin and ACE activities. Intrinsic fluorescence intensity data showed that LY and RALP have stronger binding effects on ACE molecule compared to that of TF. LY and RALP showed the highest inhibition of ACE and renin activities, respectively. Circular dichroism data showed that the inhibitory mechanism involved extensive peptide-dependent reductions in α-helix and β-sheet fractions of ACE and renin protein conformations. Molecular docking studies confirmed that the higher renin-inhibitory activity of RALP may be due to formation of several hydrogen bonds (H-bonds) with the enzyme’s active site residues. The rapeseed peptides inhibited renin and ACE activities mostly through binding to enzyme active site or non-active sites and forming extensive H-bonds that distorted the normal configuration required for catalysis. Data presented from this work could enhance development of highly potent antihypertensive natural peptides or peptidomimetics. Public Library of Science 2014-03-06 /pmc/articles/PMC3946342/ /pubmed/24603692 http://dx.doi.org/10.1371/journal.pone.0091051 Text en © 2014 He et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article He, Rong Aluko, Rotimi E. Ju, Xing-Rong Evaluating Molecular Mechanism of Hypotensive Peptides Interactions with Renin and Angiotensin Converting Enzyme |
title | Evaluating Molecular Mechanism of Hypotensive Peptides Interactions with Renin and Angiotensin Converting Enzyme |
title_full | Evaluating Molecular Mechanism of Hypotensive Peptides Interactions with Renin and Angiotensin Converting Enzyme |
title_fullStr | Evaluating Molecular Mechanism of Hypotensive Peptides Interactions with Renin and Angiotensin Converting Enzyme |
title_full_unstemmed | Evaluating Molecular Mechanism of Hypotensive Peptides Interactions with Renin and Angiotensin Converting Enzyme |
title_short | Evaluating Molecular Mechanism of Hypotensive Peptides Interactions with Renin and Angiotensin Converting Enzyme |
title_sort | evaluating molecular mechanism of hypotensive peptides interactions with renin and angiotensin converting enzyme |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946342/ https://www.ncbi.nlm.nih.gov/pubmed/24603692 http://dx.doi.org/10.1371/journal.pone.0091051 |
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