MOLECULAR MODELING OF INTERACTIONS OF AGITOXIN 2 WITH VOLTAGE-GATED POTASSIUM CHANNEL Kv1.3
Abstract
Voltage-gated potassium channel Kv1.3 is involved in a number of processes in excitable and non-excitable cells: maintenance of resting membrane potential, transfer of signals, apoptosis, regulation of cell volume, activation and proliferation of white blood cells. Blocking this channel is an effective approach for the treatment of autoimmune, oncological, chronic inflammatory and metabolic diseases. The most prospective blockers of Kv1.3 are toxins isolated from the venom of scorpions. Knowledge of the molecular aspects of binding of peptide blockers with channel is an important condition for the creation of highly effective and selective ligands. In the present work a complex of hybrid channel KcsA-Kv1.3 with agitoxin 2 was built using homology modeling and molecular dynamics simulation. Analysis of formed contacts allowed us to reveal a complete pattern of interactions and to identify key residues that are responsible for the toxin binding affinity. Results of computational experiment are consistent with the experimental data and important for drug development.
About the Authors
A. D. Volyntseva
Lomonosov Moscow State University
Russian Federation
Russian Federation
Department of Bioengineering, School of Biology,
Leninskiye gory 1-12, Moscow, 119234
V. N. Novoseletsky
Lomonosov Moscow State University
Russian Federation
Russian Federation
Department of Bioengineering, School of Biology,
Leninskiye gory 1-12, Moscow, 119234
K. V. Shaitan
Lomonosov Moscow State University
Russian Federation
Russian Federation
Department of Bioengineering, School of Biology,
Leninskiye gory 1-12, Moscow, 119234
A. V. Feofanov
Lomonosov Moscow State University
Russian Federation
Russian Federation
Department of Bioengineering, School of Biology,
Leninskiye gory 1-12, Moscow, 119234
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Review
For citations:
Volyntseva A.D., Novoseletsky V.N., Shaitan K.V., Feofanov A.V. MOLECULAR MODELING OF INTERACTIONS OF AGITOXIN 2 WITH VOLTAGE-GATED POTASSIUM CHANNEL Kv1.3. Vestnik Moskovskogo universiteta. Seriya 16. Biologiya. 2017;72(1):29-34. (In Russ.)
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