Interaction of cardiac troponin with cardiotonic drugs: A structural perspective
Interaction of cardiac troponin with cardiotonic drugs: A structural perspective
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DOI：
10.1016/j.bbrc.2007.12.108
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发表时间：
2008-04-25
影响因子：
3.1
通讯作者：
Sykes, Brian D.
中科院分区：
文献类型：
--
作者：
Li, Monica X.;Robertson, Ian M.;Sykes, Brian D.
自其发现以来的40年中，许多研究都集中在了解肌钙蛋白作为肌丝分子开关在调节横纹肌收缩的Ca 2+依赖性激活中的作用。最近，研究探索了心肌肌钙蛋白作为强心剂靶点的作用。这些药物在临床上可用于治疗心力衰竭，即心脏不再能够向其他器官泵送足够的血液的情况。这些药物通过调节肌钙蛋白的Ca 2+敏感性的机制起作用;这种作用模式在治疗上是理想的，因为细胞内Ca 2+浓度不受干扰，保留了其他基于Ca 2+的信号传导途径的调节。本文综述了心肌肌钙蛋白与各种强心药物相互作用的分子细节。我们目前最近的结构工作，已经确定了对接网站的几种强心药物的肌钙蛋白C-肌钙蛋白I接口，并讨论其相关性的设计肌钙蛋白为基础的药物治疗心脏病。(c)2007年爱思唯尔公司All rights reserved.
Over 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 Ca2+-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 Ca2+-sensitivity of troponin; such a mode of action is therapeutically desirable because intracellular Ca2+ concentration is not perturbed, preserving the regulation of other Ca2+-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. (c) 2007 Elsevier Inc. All rights reserved.