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Mechanisms of Action of Eg5 Inhibitors

  • Robert A. CrossEmail author
Chapter

Abstract

Many inhibitors have now been described that bind specifically to Eg5. It is clear that inhibition is allosteric and that the binding of inhibitors influences motor activity largely by influencing the dynamics of nucleotide exchange, but surprisingly, whilst the residue requirements in the motor and the structure-activity relationships for the inhibitors have been examined by several groups, the allosteric molecular mechanisms by which inhibitors inhibit nucleotide exchange at the active site have not been widely discussed. The conformational cycle of the Eg5 motor is increasingly well understood, and understanding exactly how this cycle is arrested by inhibitors is an important problem. Here I briefly review current evidence on the structural mechanisms by which allosteric Eg5 inhibitors inhibit motor activity. I suggest that current Eg5 inhibitors work predominantly by stabilising the active site Mg2+ ion, and that they do this by stabilising the loop L5 in an apo-like conformation.

Keywords

Salt Bridge Inhibited State Motor Head Global Conformation Drug Binding Pocket 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  1. 1.Warwick Medical SchoolCoventryUK

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