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

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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Bibliographic Details
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
Description
Summary: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.
ISSN:1475-6366
1475-6374

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