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Structural Basis of pH Dependence of Neoculin, a Sweet Taste-Modifying Protein

Among proteins utilized as sweeteners, neoculin and miraculin are taste-modifying proteins that exhibit pH-dependent sweetness. Several experiments on neoculin have shown that His11 of neoculin is responsible for pH dependence. We investigated the molecular mechanism of the pH dependence of neoculin...

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Autores principales: Ohkubo, Takayuki, Tamiya, Minoru, Abe, Keiko, Ishiguro, Masaji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444330/
https://www.ncbi.nlm.nih.gov/pubmed/26010443
http://dx.doi.org/10.1371/journal.pone.0126921
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author Ohkubo, Takayuki
Tamiya, Minoru
Abe, Keiko
Ishiguro, Masaji
author_facet Ohkubo, Takayuki
Tamiya, Minoru
Abe, Keiko
Ishiguro, Masaji
author_sort Ohkubo, Takayuki
collection PubMed
description Among proteins utilized as sweeteners, neoculin and miraculin are taste-modifying proteins that exhibit pH-dependent sweetness. Several experiments on neoculin have shown that His11 of neoculin is responsible for pH dependence. We investigated the molecular mechanism of the pH dependence of neoculin by molecular dynamics (MD) calculations. The MD calculations for the dimeric structures of neoculin and His11 mutants showed no significant structural changes for each monomer at neutral and acidic pH levels. The dimeric structure of neoculin dissociated to form isolated monomers under acidic conditions but was maintained at neutral pH. The dimeric structure of the His11Ala mutant, which is sweet at both neutral and acidic pH, showed dissociation at both pH 3 and 7. The His11 residue is located at the interface of the dimer in close proximity to the Asp91 residue of the other monomer. The MD calculations for His11Phe and His11Tyr mutants demonstrated the stability of the dimeric structures at neutral pH and the dissociation of the dimers to isolated monomers. The dissociation of the dimer caused a flexible backbone at the surface that was different from the dimeric interface at the point where the other monomer interacts to form an oligomeric structure. Further MD calculations on the tetrameric structure of neoculin suggested that the flexible backbone contributed to further dissociation of other monomers under acidic conditions. These results suggest that His11 plays a role in the formation of oligomeric structures at pH 7 and that the isolated monomer of neoculin at acidic pH is responsible for sweetness.
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spelling pubmed-44443302015-06-16 Structural Basis of pH Dependence of Neoculin, a Sweet Taste-Modifying Protein Ohkubo, Takayuki Tamiya, Minoru Abe, Keiko Ishiguro, Masaji PLoS One Research Article Among proteins utilized as sweeteners, neoculin and miraculin are taste-modifying proteins that exhibit pH-dependent sweetness. Several experiments on neoculin have shown that His11 of neoculin is responsible for pH dependence. We investigated the molecular mechanism of the pH dependence of neoculin by molecular dynamics (MD) calculations. The MD calculations for the dimeric structures of neoculin and His11 mutants showed no significant structural changes for each monomer at neutral and acidic pH levels. The dimeric structure of neoculin dissociated to form isolated monomers under acidic conditions but was maintained at neutral pH. The dimeric structure of the His11Ala mutant, which is sweet at both neutral and acidic pH, showed dissociation at both pH 3 and 7. The His11 residue is located at the interface of the dimer in close proximity to the Asp91 residue of the other monomer. The MD calculations for His11Phe and His11Tyr mutants demonstrated the stability of the dimeric structures at neutral pH and the dissociation of the dimers to isolated monomers. The dissociation of the dimer caused a flexible backbone at the surface that was different from the dimeric interface at the point where the other monomer interacts to form an oligomeric structure. Further MD calculations on the tetrameric structure of neoculin suggested that the flexible backbone contributed to further dissociation of other monomers under acidic conditions. These results suggest that His11 plays a role in the formation of oligomeric structures at pH 7 and that the isolated monomer of neoculin at acidic pH is responsible for sweetness. Public Library of Science 2015-05-26 /pmc/articles/PMC4444330/ /pubmed/26010443 http://dx.doi.org/10.1371/journal.pone.0126921 Text en © 2015 Ohkubo 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
Ohkubo, Takayuki
Tamiya, Minoru
Abe, Keiko
Ishiguro, Masaji
Structural Basis of pH Dependence of Neoculin, a Sweet Taste-Modifying Protein
title Structural Basis of pH Dependence of Neoculin, a Sweet Taste-Modifying Protein
title_full Structural Basis of pH Dependence of Neoculin, a Sweet Taste-Modifying Protein
title_fullStr Structural Basis of pH Dependence of Neoculin, a Sweet Taste-Modifying Protein
title_full_unstemmed Structural Basis of pH Dependence of Neoculin, a Sweet Taste-Modifying Protein
title_short Structural Basis of pH Dependence of Neoculin, a Sweet Taste-Modifying Protein
title_sort structural basis of ph dependence of neoculin, a sweet taste-modifying protein
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444330/
https://www.ncbi.nlm.nih.gov/pubmed/26010443
http://dx.doi.org/10.1371/journal.pone.0126921
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