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Molecular Dynamics Driven Design of pH-Stabilized Mutants of MNEI, a Sweet Protein
MNEI is a single chain derivative of monellin, a plant protein that can interact with the human sweet taste receptor, being therefore perceived as sweet. This unusual physiological activity makes MNEI a potential template for the design of new sugar replacers for the food and beverage industry. Unfo...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920389/ https://www.ncbi.nlm.nih.gov/pubmed/27340829 http://dx.doi.org/10.1371/journal.pone.0158372 |
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author | Leone, Serena Picone, Delia |
author_facet | Leone, Serena Picone, Delia |
author_sort | Leone, Serena |
collection | PubMed |
description | MNEI is a single chain derivative of monellin, a plant protein that can interact with the human sweet taste receptor, being therefore perceived as sweet. This unusual physiological activity makes MNEI a potential template for the design of new sugar replacers for the food and beverage industry. Unfortunately, applications of MNEI have been so far limited by its intrinsic sensitivity to some pH and temperature conditions, which could occur in industrial processes. Changes in physical parameters can, in fact, lead to irreversible protein denaturation, as well as aggregation and precipitation. It has been previously shown that the correlation between pH and stability in MNEI derives from the presence of a single glutamic residue in a hydrophobic pocket of the protein. We have used molecular dynamics to study the consequences, at the atomic level, of the protonation state of such residue and have identified the network of intramolecular interactions responsible for MNEI stability at acidic pH. Based on this information, we have designed a pH-independent, stabilized mutant of MNEI and confirmed its increased stability by both molecular modeling and experimental techniques. |
format | Online Article Text |
id | pubmed-4920389 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-49203892016-07-18 Molecular Dynamics Driven Design of pH-Stabilized Mutants of MNEI, a Sweet Protein Leone, Serena Picone, Delia PLoS One Research Article MNEI is a single chain derivative of monellin, a plant protein that can interact with the human sweet taste receptor, being therefore perceived as sweet. This unusual physiological activity makes MNEI a potential template for the design of new sugar replacers for the food and beverage industry. Unfortunately, applications of MNEI have been so far limited by its intrinsic sensitivity to some pH and temperature conditions, which could occur in industrial processes. Changes in physical parameters can, in fact, lead to irreversible protein denaturation, as well as aggregation and precipitation. It has been previously shown that the correlation between pH and stability in MNEI derives from the presence of a single glutamic residue in a hydrophobic pocket of the protein. We have used molecular dynamics to study the consequences, at the atomic level, of the protonation state of such residue and have identified the network of intramolecular interactions responsible for MNEI stability at acidic pH. Based on this information, we have designed a pH-independent, stabilized mutant of MNEI and confirmed its increased stability by both molecular modeling and experimental techniques. Public Library of Science 2016-06-24 /pmc/articles/PMC4920389/ /pubmed/27340829 http://dx.doi.org/10.1371/journal.pone.0158372 Text en © 2016 Leone, Picone http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Leone, Serena Picone, Delia Molecular Dynamics Driven Design of pH-Stabilized Mutants of MNEI, a Sweet Protein |
title | Molecular Dynamics Driven Design of pH-Stabilized Mutants of MNEI, a Sweet Protein |
title_full | Molecular Dynamics Driven Design of pH-Stabilized Mutants of MNEI, a Sweet Protein |
title_fullStr | Molecular Dynamics Driven Design of pH-Stabilized Mutants of MNEI, a Sweet Protein |
title_full_unstemmed | Molecular Dynamics Driven Design of pH-Stabilized Mutants of MNEI, a Sweet Protein |
title_short | Molecular Dynamics Driven Design of pH-Stabilized Mutants of MNEI, a Sweet Protein |
title_sort | molecular dynamics driven design of ph-stabilized mutants of mnei, a sweet protein |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920389/ https://www.ncbi.nlm.nih.gov/pubmed/27340829 http://dx.doi.org/10.1371/journal.pone.0158372 |
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