RH421 binds into the ATP-binding site on the Na/K-ATPase.

The Na/K-ATPase plays a key role in ion transport across the plasma membrane of all animal cells. The voltage-sensitive styrylpyrimidium dye RH421 has been used in several laboratories for monitoring of Na/K-ATPase kinetics. It is known, that RH421 can interact with the enzyme and it can influence its activity at micromolar concentrations, but structural details of this interaction are only poorly understood.

Crystals of Na(+)/K(+)-ATPase with bound cisplatin.

Cisplatin is the most widely used chemotherapeutics for cancer treatment, however, its administration is connected to inevitable adverse effects. Previous studies suggested that cisplatin is able to inhibit Na(+)/K(+)-ATPase (NKA), the enzyme responsible for maintaining electrochemical potential and sodium gradient across the plasma membrane. Here we report a crystallographic analysis of cisplatin bound to NKA in the ouabain bound E2P form.

Na(+)/K(+)-ATPase inhibition by cisplatin and consequences for cisplatin nephrotoxicity.

Aims: Cisplatin is a widely used chemotherapeutic. However, it is associated with numerous adverse effects. The aim of our study was examination of cisplatin interaction with Na(+)/K(+)-ATPase (NKA, the sodium pump).

Fluorone dyes have binding sites on both cytoplasmic and extracellular domains of Na,K-ATPase.

Combination of fluorescence techniques and molecular docking was used to monitor interaction of Na,K-ATPase and its large cytoplasmic loop connecting fourth and fifth transmembrane helices (C45) with fluorone dyes (i.e. eosin Y, 5(6)-carboxyeosin, rose bengal, fluorescein, and erythrosine B).

Covalent binding of cisplatin impairs the function of Na(+)/K(+)-ATPase by binding to its cytoplasmic part.

This study was aimed at verifying the hypothesis that acute kidney failure accompanying cisplatin administration in the cancer therapy could be due to cisplatin interaction with the cytoplasmic part of Na(+)/K(+)-ATPase. Our results demonstrated that cisplatin-binding caused inhibition of Na(+)/K(+)-ATPase, in contrast to other platinated chemotherapeutics such as carboplatin and oxaliplatin, which are known to be much less nephrotoxic. To acquire more detailed structural information, we performed a series of experiments with the isolated large cytoplasmic segment connecting transmembrane helices 4 and 5 (C45 loop) of Na(+)/K(+)-ATPase.