Identification of cisplatin-binding sites on the large cytoplasmic loop of the Na(+)/K(+)-ATPase

Cisplatin is the most widely used chemotherapeutic drug for the treatment of various types of cancer; however, its administration brings also numerous side effects. It was demonstrated that cisplatin can inhibit the Na(+)/K(+)-ATPase (NKA), which can explain a large part of the adverse effects. In t...

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Autores principales: Šeflová, Jaroslava, Čechová, Petra, Štenclová, Tereza, Šebela, Marek, Kubala, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2018
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009960/
https://www.ncbi.nlm.nih.gov/pubmed/29577756
http://dx.doi.org/10.1080/14756366.2018.1445735
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author Šeflová, Jaroslava
Čechová, Petra
Štenclová, Tereza
Šebela, Marek
Kubala, Martin
author_facet Šeflová, Jaroslava
Čechová, Petra
Štenclová, Tereza
Šebela, Marek
Kubala, Martin
author_sort Šeflová, Jaroslava
collection PubMed
description Cisplatin is the most widely used chemotherapeutic drug for the treatment of various types of cancer; however, its administration brings also numerous side effects. It was demonstrated that cisplatin can inhibit the Na(+)/K(+)-ATPase (NKA), which can explain a large part of the adverse effects. In this study, we have identified five cysteinyl residues (C452, C456, C457, C577, and C656) as the cisplatin binding sites on the cytoplasmic loop connecting transmembrane helices 4 and 5 (C45), using site-directed mutagenesis and mass spectrometry experiments. The identified residues are known to be susceptible to glutathionylation indicating their involvement in a common regulatory mechanism.
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spelling pubmed-60099602018-07-11 Identification of cisplatin-binding sites on the large cytoplasmic loop of the Na(+)/K(+)-ATPase Šeflová, Jaroslava Čechová, Petra Štenclová, Tereza Šebela, Marek Kubala, Martin J Enzyme Inhib Med Chem Research Paper Cisplatin is the most widely used chemotherapeutic drug for the treatment of various types of cancer; however, its administration brings also numerous side effects. It was demonstrated that cisplatin can inhibit the Na(+)/K(+)-ATPase (NKA), which can explain a large part of the adverse effects. In this study, we have identified five cysteinyl residues (C452, C456, C457, C577, and C656) as the cisplatin binding sites on the cytoplasmic loop connecting transmembrane helices 4 and 5 (C45), using site-directed mutagenesis and mass spectrometry experiments. The identified residues are known to be susceptible to glutathionylation indicating their involvement in a common regulatory mechanism. Taylor & Francis 2018-03-26 /pmc/articles/PMC6009960/ /pubmed/29577756 http://dx.doi.org/10.1080/14756366.2018.1445735 Text en © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Šeflová, Jaroslava
Čechová, Petra
Štenclová, Tereza
Šebela, Marek
Kubala, Martin
Identification of cisplatin-binding sites on the large cytoplasmic loop of the Na(+)/K(+)-ATPase
title Identification of cisplatin-binding sites on the large cytoplasmic loop of the Na(+)/K(+)-ATPase
title_full Identification of cisplatin-binding sites on the large cytoplasmic loop of the Na(+)/K(+)-ATPase
title_fullStr Identification of cisplatin-binding sites on the large cytoplasmic loop of the Na(+)/K(+)-ATPase
title_full_unstemmed Identification of cisplatin-binding sites on the large cytoplasmic loop of the Na(+)/K(+)-ATPase
title_short Identification of cisplatin-binding sites on the large cytoplasmic loop of the Na(+)/K(+)-ATPase
title_sort identification of cisplatin-binding sites on the large cytoplasmic loop of the na(+)/k(+)-atpase
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009960/
https://www.ncbi.nlm.nih.gov/pubmed/29577756
http://dx.doi.org/10.1080/14756366.2018.1445735
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