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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Revisiting the kinetics of nitric oxide (NO) binding to soluble guanylate cyclase: The simple NO-binding model is incorrect
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Revisiting the kinetics of nitric oxide (NO) binding to soluble guanylate cyclase: The simple NO-binding model is incorrect

机译：回顾一氧化氮（NO）结合可溶性鸟苷酸环化酶的动力学：简单的NO结合模型是不正确的

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摘要

Soluble guanylate cyclase (sGC) is a ferrous iron hemoprotein receptor for nitric oxide (NO). NO binding to the heme activates the enzyme 300-fold. sGC as isolated is five-coordinate, ferrous with histidine as the axial ligand. The NO-activated enzyme is a five-coordinate nitrosyl complex where the axial histidine bond is broken. Past studies using rapid-reaction kinetics demonstrated that both the formation of a six-coordinate intermediate and the conversion of the intermediate to the activated five-coordinate nitrosyl complex depended on the concentration of NO. A model invoking a second NO molecule as a catalyst for the conversion of the six-coordinate intermediate to the five-coordinate sGC-NO complex was proposed to explain the observed kinetic data. A recent study [Bellamy, T. C., Wood, J. & Garthwaite, J. (2002) Proc. Watl, Acad. Sci. USA 99, 507-510] concluded that a simple two-step binding model explains the results. Here we show through further analysis and simulations of previous data that the simple two-step binding model cannot be used to describe our results. Instead we show that a slightly more complex two-step binding model, where NO is used as a ligand in the first step and a catalyst in the second step, can describe our results quite satisfactorily. These new simulations combined with the previous activation data lead to the conclusion that the intermediate six-coordinate sGC-NO complex has substantial activity. The model derived from our simulations also can account for the slow deactivation of sGC that has been observed in vitro.
机译：可溶性鸟苷酸环化酶（sGC）是一氧化氮（NO）的亚铁血红蛋白受体。没有结合血红素激活酶300倍。分离的sGC为五配位亚铁，以组氨酸为轴向配体。 NO激活的酶是一个五配位的亚硝酰基复合物，其中的轴向组氨酸键断裂。过去使用快速反应动力学的研究表明，六配位中间体的形成以及中间体向活化的五配位亚硝酰基配合物的转化均取决于NO的浓度。提出了一个模型，该模型调用第二个NO分子作为催化剂，将六坐标中间物转化为五坐标sGC-NO配合物，以解释观察到的动力学数据。最近的一项研究[Bellamy，T. C.，Wood，J.＆Garthwaite，J.（2002）Proc。 Watl，Acad。科学[USA 99，507-510]得出结论，简单的两步绑定模型可以解释结果。在这里，我们通过对先前数据的进一步分析和模拟表明，简单的两步绑定模型无法用于描述我们的结果。取而代之的是，我们显示了一个稍微复杂的两步结合模型，其中第一步使用NO作为配体，第二步使用催化剂，可以令人满意地描述我们的结果。这些新的模拟与先前的激活数据相结合得出结论，即中间的六坐标sGC-NO复合物具有大量活性。从我们的模拟中得出的模型也可以解释体外观察到的sGC缓慢失活。

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