Molecular modeling elucidates the cellular mechanism of synaptotagmin-SNARE inhibition: a novel plausible route to anti-wrinkle activity of botox-like cosmetic active molecules

© 2017 Springer Science+Business Media, LLC Synaptotagmin 1 (Syt1) is the Ca 2+ sensor protein with an essential role in neurotransmitter release. Since the wrinkle formation is due to the excessive muscle fiber stimulation in the face, a helpful stratagem to diminish the wrinkle line intenseness is...

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Main Authors: Pathomwat Wongrattanakamon, Piyarat Nimmanpipug, Busaban Sirithunyalug, Supat Jiranusornkul
Format: Journal
Published: 2018
Online Access:https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85030865999&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/43581
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Institution: Chiang Mai University
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spelling th-cmuir.6653943832-435812018-01-24T03:50:20Z Molecular modeling elucidates the cellular mechanism of synaptotagmin-SNARE inhibition: a novel plausible route to anti-wrinkle activity of botox-like cosmetic active molecules Pathomwat Wongrattanakamon Piyarat Nimmanpipug Busaban Sirithunyalug Supat Jiranusornkul © 2017 Springer Science+Business Media, LLC Synaptotagmin 1 (Syt1) is the Ca 2+ sensor protein with an essential role in neurotransmitter release. Since the wrinkle formation is due to the excessive muscle fiber stimulation in the face, a helpful stratagem to diminish the wrinkle line intenseness is to weaken the innervating neuron activity through Syt1 inhibition which is one of the possible therapeutic strategies against wrinkles. Recently, experimental evidence showed that botox-like peptides, which are typically used as SNARE modulators, may inhibit Syt1. In this work, we applied molecular modeling to (1) characterize the structural framework and (2) define the atomistic information of the factors for the inhibition mechanism. The modeling identified the plausible binding cleft able to efficiently bind all botox-like peptides. The MD simulations revealed that all peptides induced significant Syt1 rigidity by binding in the cleft of the C2A–C2B interface. The consequence of this binding event is the suppression of the protein motion associated with conformational change of Syt1 from the closed form to the open form. On this basis, this finding may therefore be of subservience for the advancement of novel botox-like molecules for the therapeutic treatment of wrinkle, targeting and modulating the function of Syt1. 2018-01-24T03:50:20Z 2018-01-24T03:50:20Z 2017-10-10 Journal 15734919 03008177 2-s2.0-85030865999 10.1007/s11010-017-3196-5 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85030865999&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/43581
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
description © 2017 Springer Science+Business Media, LLC Synaptotagmin 1 (Syt1) is the Ca 2+ sensor protein with an essential role in neurotransmitter release. Since the wrinkle formation is due to the excessive muscle fiber stimulation in the face, a helpful stratagem to diminish the wrinkle line intenseness is to weaken the innervating neuron activity through Syt1 inhibition which is one of the possible therapeutic strategies against wrinkles. Recently, experimental evidence showed that botox-like peptides, which are typically used as SNARE modulators, may inhibit Syt1. In this work, we applied molecular modeling to (1) characterize the structural framework and (2) define the atomistic information of the factors for the inhibition mechanism. The modeling identified the plausible binding cleft able to efficiently bind all botox-like peptides. The MD simulations revealed that all peptides induced significant Syt1 rigidity by binding in the cleft of the C2A–C2B interface. The consequence of this binding event is the suppression of the protein motion associated with conformational change of Syt1 from the closed form to the open form. On this basis, this finding may therefore be of subservience for the advancement of novel botox-like molecules for the therapeutic treatment of wrinkle, targeting and modulating the function of Syt1.
format Journal
author Pathomwat Wongrattanakamon
Piyarat Nimmanpipug
Busaban Sirithunyalug
Supat Jiranusornkul
spellingShingle Pathomwat Wongrattanakamon
Piyarat Nimmanpipug
Busaban Sirithunyalug
Supat Jiranusornkul
Molecular modeling elucidates the cellular mechanism of synaptotagmin-SNARE inhibition: a novel plausible route to anti-wrinkle activity of botox-like cosmetic active molecules
author_facet Pathomwat Wongrattanakamon
Piyarat Nimmanpipug
Busaban Sirithunyalug
Supat Jiranusornkul
author_sort Pathomwat Wongrattanakamon
title Molecular modeling elucidates the cellular mechanism of synaptotagmin-SNARE inhibition: a novel plausible route to anti-wrinkle activity of botox-like cosmetic active molecules
title_short Molecular modeling elucidates the cellular mechanism of synaptotagmin-SNARE inhibition: a novel plausible route to anti-wrinkle activity of botox-like cosmetic active molecules
title_full Molecular modeling elucidates the cellular mechanism of synaptotagmin-SNARE inhibition: a novel plausible route to anti-wrinkle activity of botox-like cosmetic active molecules
title_fullStr Molecular modeling elucidates the cellular mechanism of synaptotagmin-SNARE inhibition: a novel plausible route to anti-wrinkle activity of botox-like cosmetic active molecules
title_full_unstemmed Molecular modeling elucidates the cellular mechanism of synaptotagmin-SNARE inhibition: a novel plausible route to anti-wrinkle activity of botox-like cosmetic active molecules
title_sort molecular modeling elucidates the cellular mechanism of synaptotagmin-snare inhibition: a novel plausible route to anti-wrinkle activity of botox-like cosmetic active molecules
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85030865999&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/43581
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