1Department of Biophysics, P. J. Safarik University,
Jesenna 5, 041 54 Kosice, Slovak Republic (http://bioflab.upjs.sk)
2Department of Physical Chemistry, Arrhenius Laboratory, Stockholm University, Sweden
3International Laser Centre, Ilkovicova 3, 812 19
Bratislava, Slovak Republic
Protein kinase C (PKC), a family of serine/threonine kinases, is intimately involved in the regulation of a variety of cellular functions such as gene expression, cellular growth and differentiation. PKC is regulated by two distinct mechanisms: by binding 3 molecules of ATP which regulates the active site and subcellular localization of the enzyme, and by second messengers (Ca2+, diacylglycerol, phorbol esters) which promote PKC's membrane association and result to pseudosubstrate exposure. Phorbol 12-myristate-13-acetate (PMA), powerful tumor-promoting agent, binds to the Cys1 and Cys2 domain in PKC on membrane surface with nanomolar binding affinity. Molecular modelling  was used for the study of PMA+dipalmitoylphosphatidylcholine (DPPC) bilayer and Cys2+PMA+DPPC bilayer complexes. Function of hydrophobic and hydrogen bond interactions between PMA and Cys2 domainin is discussed. Comparison with existing experimental data showed that obtained molecular model of Cys2 domain with its activator PMA on membrane surface is consistent with existing X-ray  and NMR  results.
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