Natalya U. Fedosova

Research

Background
The overall aim of our investigations is to understand the mechanism of energy transduction in Na,K-ATPase in particular and in P-type ATPases in general. The Na,K-ATPase, our preferred object, is a primary active transporter that exports sodium out of the cell and imports potassium at the expense of ATP. The created ion gradients are critical for muscle contraction, neuronal excitability, volume regulation and many other cellular functions, and the pump activity stays for up to 30% of the daily energy consumption.

In the past few years our attention has been mainly focused on the Na,K-ATPase interactions with its specific inhibitors, the cardiotonic steroids. Recently these studies were extended to Ca-ATPase and its specific inhibitor thapsigargin with the ambition to investigate the feasibility of P-type ATPases as drug targets. The first step is to establish the correlation between the mechanism behind the inhibition of the enzymatic reaction by various inhibitor analogs and the structural data obtained by X-ray diffraction analysis of the corresponding enzyme complexes. The second step will be to describe the interplay between P-ATPases and other cellular components such as channels and transporters, apoptotic and other biochemical effectors, by the use of in vivo systems (cell lines, tissue samples) in order to understand the mechanism of inhibitor action at the cellular level.

Research interests

  • Structure-function relationships in P-type ATPases
  • Specific inhibitors of P-type ATPases as prototypes for the development of new drugs. Mechanisms behind their pharmacological application.
  • Protein-lipid interactions

Methodologies

  • Purification of membrane proteins
  • Characterization of their functional activity by various biochemical and biophysical methods
  • Characterization of protein structure (MALS, fluorescence, crystallization)

Collaborators and centres

N.U. Fedosova is member of Centre for Membrane Pumps in Cells and Disease funded by the Danish National Research Foundation.

Collaborators:

  • Mikael Esmann, Department of Biomedicine, Health, AU
  • Jesper Vuust Møller, Department of Biomedicine, Health, AU
  • Poul Nissen, Science and Technology, AU
  • Henrik Hellingsø Jensen, Science and Technology, AU
  • Søren Brøgger Christensen, Faculty of Pharmaceutical Sciences, KU
  • Jan Koenderink, Radboud University Nijmegen Medical Centre, The Netherlands
  • Natalia Prevarskaya, Université de Lille 1, France

Research group members

  • Mette Laursen, PhD-student
  • Charlotte Dubois, PhD-student
  • Pankaj Sehgal, postdoc
  • Birthe Bjerring Jensen, technician

Group leader

Flemming Cornelius

Professor with Special Responsibilities
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Publications

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