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Interaction of cardiac troponin with cardiotonic drugs: a structural perspective Li MX; Robertson IM; Sykes BDBiochem Biophys Res Commun 2008[Apr]; 369 (1): 88-99Over the 40 years since its discovery, many studies have focused on understanding the role of troponin as a myofilament based molecular switch in regulating the Ca(2+)-dependent activation of striated muscle contraction. Recently, studies have explored the role of cardiac troponin as a target for cardiotonic agents. These drugs are clinically useful for treating heart failure, a condition in which the heart is no longer able to pump enough blood to other organs. These agents act via a mechanism that modulates the Ca(2+)-sensitivity of troponin; such a mode of action is therapeutically desirable because intracellular Ca(2+) concentration is not perturbed, preserving the regulation of other Ca(2+)-based signaling pathways. This review describes molecular details of the interaction of cardiac troponin with a variety of cardiotonic drugs. We present recent structural work that has identified the docking sites of several cardiotonic drugs in the troponin C-troponin I interface and discuss their relevance in the design of troponin based drugs for the treatment of heart disease.|Animals[MESH]|Calcium Signaling/drug effects[MESH]|Calcium/*metabolism[MESH]|Cardiotonic Agents/*administration & dosage/chemistry/*pharmacokinetics[MESH]|Heart Diseases/*drug therapy/*metabolism[MESH]|Heart/drug effects/*physiopathology[MESH]|Humans[MESH]|Myocardial Contraction/drug effects[MESH]|Structure-Activity Relationship[MESH]|Troponin/chemistry/*metabolism[MESH] |
