Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Leone, Serena, Picone, Delia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
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
_version_ 1782439384797151232
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
work_keys_str_mv AT leoneserena moleculardynamicsdrivendesignofphstabilizedmutantsofmneiasweetprotein
AT piconedelia moleculardynamicsdrivendesignofphstabilizedmutantsofmneiasweetprotein