2-Deoxy-ATP Enhances Multiple Kinetic Parameters to Improve Cardiac Function

Abstract

and are implicated in many neurological disorders. Available x-ray structures of prokaryotic and eukaryotic Cys-loop receptors provide tremendous insights into the binding of agonists, the subsequent opening of the ion channel, and the mechanism of channel activation [1][2][3][4][5][6][7][8] . Yet the mechanism of inactivation by antagonists remains unknown. Here we present a 3.0 Å x-ray structure of the human glycine receptor a3 homopentamer in complex with a high affinity, high specificity antagonist strychnine. Our structure allows us to explore in great detail the molecular recognition of antagonists. Comparisons with previous structures reveal a mechanism of inactivating Cys-loop receptors by antagonist binding.This work has been published in Nature Sep 28.

Translation of Cardiac Myosin Activation With 2-Deoxy-ATP to Treat Heart Failure Via an Experimental Ribonucleotide Reductase-Based Gene Therapy

“…Recently reported data from an independent group showed dATP increased myosin-actin sliding velocities by 40%, and increased ATPase activity, ADP release rates, and actin-binding affinities(35). …”