可溶性鸟苷酸环化酶介导NO信号转导的结构基础及其分子机制研究

Structural basis and molecular mechanism of soluble guanylate cyclase in NO-signaling transduction

可溶性鸟苷酸环化酶(sGC)是NO信号转导通路中的核心金属酶,是NO的敏感器和受体.sGC含有?和?两个亚基,每个亚基分别具有3个结构域,包括血红素结构域、中心结构域和催化结构域,两个亚基的血红素结构域共享有一个血红素,NO结合到sGC的血红素后,激活sGC,催化其底物GTP转化为二级信号分子cGMP,开启PKG信号通路,导致血管舒张.NO信号转导通路异常将导致多种疾病的发生,如多种心血管疾病、肺动脉高血压、心力衰竭及神经退行性疾病等.近20年来,关于sGC的结构、功能、激活机制及其在生理与病理中的作用有了很多进展.本文重点对sGC的结构、功能及其活化/失活机制研究进展进行综述.

Soluble guanylatecyclase （sGC）, as a NO receptor, is a key metalloenzyme in mediating NO-signaling transduction, sGC is activated by NO to catalyze the conversion of guanosine 5＇-triphosphate （GTP） to cyclic guanylate monophosphate （cGMP）. The dysfunction of NO signaling results in many pathological disorders, including several cardiovascular diseases such as arterial hypertension, pulmonary hypertension, heart failure and so on. Significant advances in its structure, function, mechanism, and physiological ＆ pathological roles have been made throughout the past fifteen years. We herein review the progress of sGC on structural, functional investigations, as well as the proposed activation/deactivationmechanism. The heme-dependent sGC stimulators and heme- independent sGC activators have also been summarized briefly.