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Dynamic Scenario of Membrane Binding Process of Kalata B1

Kalata B1 (kB1), a cyclotide that has been used in medical applications, displays cytotoxicity related to membrane binding and oligomerization. Our molecular dynamics simulation results demonstrate that Trp19 in loop 5 of both monomeric and tetrameric kB1 is a key residue for initial anchoring in th...

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Autores principales: Nawae, Wanapinun, Hannongbua, Supa, Ruengjitchatchawalya, Marasri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4256454/
https://www.ncbi.nlm.nih.gov/pubmed/25473840
http://dx.doi.org/10.1371/journal.pone.0114473
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author Nawae, Wanapinun
Hannongbua, Supa
Ruengjitchatchawalya, Marasri
author_facet Nawae, Wanapinun
Hannongbua, Supa
Ruengjitchatchawalya, Marasri
author_sort Nawae, Wanapinun
collection PubMed
description Kalata B1 (kB1), a cyclotide that has been used in medical applications, displays cytotoxicity related to membrane binding and oligomerization. Our molecular dynamics simulation results demonstrate that Trp19 in loop 5 of both monomeric and tetrameric kB1 is a key residue for initial anchoring in the membrane binding process. This residue also facilitates the formation of kB1 tetramers. Additionally, we elucidate that kB1 preferentially binds to the membrane interfacial zone and is unable to penetrate into the membrane. In particular, significant roles of amino acid residues in loop 5 and loop 6 on the localization of kB1 to this membrane-water interface zone are found. This study reveals the roles of amino acid residues in the bioactivity of kB1, which is information that can be useful for designing new therapeutic cyclotides with less toxicity.
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spelling pubmed-42564542014-12-11 Dynamic Scenario of Membrane Binding Process of Kalata B1 Nawae, Wanapinun Hannongbua, Supa Ruengjitchatchawalya, Marasri PLoS One Research Article Kalata B1 (kB1), a cyclotide that has been used in medical applications, displays cytotoxicity related to membrane binding and oligomerization. Our molecular dynamics simulation results demonstrate that Trp19 in loop 5 of both monomeric and tetrameric kB1 is a key residue for initial anchoring in the membrane binding process. This residue also facilitates the formation of kB1 tetramers. Additionally, we elucidate that kB1 preferentially binds to the membrane interfacial zone and is unable to penetrate into the membrane. In particular, significant roles of amino acid residues in loop 5 and loop 6 on the localization of kB1 to this membrane-water interface zone are found. This study reveals the roles of amino acid residues in the bioactivity of kB1, which is information that can be useful for designing new therapeutic cyclotides with less toxicity. Public Library of Science 2014-12-04 /pmc/articles/PMC4256454/ /pubmed/25473840 http://dx.doi.org/10.1371/journal.pone.0114473 Text en © 2014 Nawae 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
Nawae, Wanapinun
Hannongbua, Supa
Ruengjitchatchawalya, Marasri
Dynamic Scenario of Membrane Binding Process of Kalata B1
title Dynamic Scenario of Membrane Binding Process of Kalata B1
title_full Dynamic Scenario of Membrane Binding Process of Kalata B1
title_fullStr Dynamic Scenario of Membrane Binding Process of Kalata B1
title_full_unstemmed Dynamic Scenario of Membrane Binding Process of Kalata B1
title_short Dynamic Scenario of Membrane Binding Process of Kalata B1
title_sort dynamic scenario of membrane binding process of kalata b1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4256454/
https://www.ncbi.nlm.nih.gov/pubmed/25473840
http://dx.doi.org/10.1371/journal.pone.0114473
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