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 this...

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Main Authors:	Jaroslava Šeflová, Petra Čechová, Tereza Štenclová, Marek Šebela, Martin Kubala
Format:	Article
Language:	English
Published:	Taylor & Francis Group 2018-01-01
Series:	Journal of Enzyme Inhibition and Medicinal Chemistry
Subjects:	Na+/K+-ATPase sodium pump C45 loop cisplatin binding site cysteine mutants
Online Access:	http://dx.doi.org/10.1080/14756366.2018.1445735

id	doaj-40f541a77e6f4b55a8637d446f818962
record_format	Article
spelling	doaj-40f541a77e6f4b55a8637d446f8189622020-11-25T01:52:52ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742018-01-0133170170610.1080/14756366.2018.14457351445735Identification of cisplatin-binding sites on the large cytoplasmic loop of the Na+/K+-ATPaseJaroslava Šeflová0Petra Čechová1Tereza Štenclová2Marek Šebela3Martin Kubala4Centre of Region Haná for Biotechnological and Agricultural Research, Palacký UniversityCentre of Region Haná for Biotechnological and Agricultural Research, Palacký UniversityCentre of Region Haná for Biotechnological and Agricultural Research, Palacký UniversityCentre of Region Haná for Biotechnological and Agricultural Research, Palacký UniversityCentre of Region Haná for Biotechnological and Agricultural Research, Palacký UniversityCisplatin 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.http://dx.doi.org/10.1080/14756366.2018.1445735Na+/K+-ATPasesodium pumpC45 loopcisplatinbinding sitecysteine mutants
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Jaroslava Šeflová Petra Čechová Tereza Štenclová Marek Šebela Martin Kubala
spellingShingle	Jaroslava Šeflová Petra Čechová Tereza Štenclová Marek Šebela Martin Kubala Identification of cisplatin-binding sites on the large cytoplasmic loop of the Na+/K+-ATPase Journal of Enzyme Inhibition and Medicinal Chemistry Na+/K+-ATPase sodium pump C45 loop cisplatin binding site cysteine mutants
author_facet	Jaroslava Šeflová Petra Čechová Tereza Štenclová Marek Šebela Martin Kubala
author_sort	Jaroslava Šeflová
title	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_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_sort	identification of cisplatin-binding sites on the large cytoplasmic loop of the na+/k+-atpase
publisher	Taylor & Francis Group
series	Journal of Enzyme Inhibition and Medicinal Chemistry
issn	1475-6366 1475-6374
publishDate	2018-01-01
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.
topic	Na+/K+-ATPase sodium pump C45 loop cisplatin binding site cysteine mutants
url	http://dx.doi.org/10.1080/14756366.2018.1445735
work_keys_str_mv	AT jaroslavaseflova identificationofcisplatinbindingsitesonthelargecytoplasmicloopofthenakatpase AT petracechova identificationofcisplatinbindingsitesonthelargecytoplasmicloopofthenakatpase AT terezastenclova identificationofcisplatinbindingsitesonthelargecytoplasmicloopofthenakatpase AT mareksebela identificationofcisplatinbindingsitesonthelargecytoplasmicloopofthenakatpase AT martinkubala identificationofcisplatinbindingsitesonthelargecytoplasmicloopofthenakatpase
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Identification of cisplatin-binding sites on the large cytoplasmic loop of the Na+/K+-ATPase

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