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.

• Klíčová slova
• C45 loop, Na+/K+-ATPase, binding site, cisplatin, cysteine mutants, sodium pump,
• MeSH
• cisplatina chemie   farmakologie   MeSH
• cystein antagonisté a inhibitory   metabolismus   MeSH
• cytoplazma účinky léků   metabolismus   MeSH
• hmotnostní spektrometrie MeSH
• mutageneze cílená MeSH
• myši MeSH
• protinádorové látky chemie   farmakologie   MeSH
• simulace molekulární dynamiky MeSH
• sodíko-draslíková ATPasa antagonisté a inhibitory   genetika   metabolismus   MeSH
• vazebná místa účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cisplatina MeSH
• cystein MeSH
• protinádorové látky MeSH
• sodíko-draslíková ATPasa MeSH