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Trends Biochem Sci. 2011 Feb;36(2):65-77. doi: 10.1016/j.tibs.2010.09.006. Epub 2010 Oct 23.

Protein kinases: evolution of dynamic regulatory proteins.

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Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093, USA.


Eukayotic protein kinases evolved as a family of highly dynamic molecules with strictly organized internal architecture. A single hydrophobic F-helix serves as a central scaffold for assembly of the entire molecule. Two non-consecutive hydrophobic structures termed "spines" anchor all the elements important for catalysis to the F-helix. They make firm, but flexible, connections within the molecule, providing a high level of internal dynamics of the protein kinase. During the course of evolution, protein kinases developed a universal regulatory mechanism associated with a large activation segment that can be dynamically folded and unfolded in the course of cell functioning. Protein kinases thus represent a unique, highly dynamic, and precisely regulated set of switches that control most biological events in eukaryotic cells.

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