BASIS OF GUANYLATE-CYCLASE ACTIVATION BY CARBON-MONOXIDE
BASIS OF GUANYLATE-CYCLASE ACTIVATION BY CARBON-MONOXIDE
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DOI：
10.1073/pnas.92.7.2568
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发表时间：
1995-03-28
影响因子：
11.1
通讯作者：
KOESLING, D
中科院分区：
文献类型：
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作者：
KHARITONOV, VG;SHARMA, VS;KOESLING, D
在pH7.5条件下，用闪光光解法研究了CO与鸟苷酸环化酶[GTP焦磷酸裂解酶（环化），EC 4，6，1，2]结合和从羧基鸟苷酸环化酶解离的动力学，在23 ℃下的速率常数为1.2 +/- 0.1 × 10（5）M（-1）。sec（-1）和28 +/-2 sec（-1）。虽然CO结合速率常数与血红蛋白的T状态相同，但CO解离速率常数远高于SIS配位碳血红素蛋白的预期;但吸收光谱表明为六配位血红素。这两个观察结果是调和的反应机制，其中CO解离进行通过一个五配位中间体。该中间体在结构上非常相似的鸟苷酸环化酶的五坐标亚硝酰血红素衍生物，大概是负责观察到的4倍激活鸟苷酸环化酶由CO。因此，我们提供了一个模型，解释酶的亚硝酰和羧基形式的酶的活性的基础上，一个共同的机制。
Kinetics of CO association with guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4,6,1,2] and dissociation from carboxy guanylate cyclase have been studied at pH 7.5 by flash photolysis, yielding rate constants at 23 degrees C of 1.2 +/- 0.1 x 10(5) M(-1). sec(-1), and 28 +/- 2 sec(-1), respectively. While the CO combination rate constant is the same as for the T state of hemoglobin, the CO dissociation rate constant is much higher than expected for a sis coordinate carboxyheme protein; yet the absorption spectrum is indicative of a six-coordinate heme. The two observations are reconciled by a reaction mechanism in which CO dissociation proceeds via a five-coordinate intermediate. This intermediate is structurally very similar to the five-coordinate nitrosyl heme derivative of guanylate cyclase and is presumably responsible for the observed 4-fold activation of guanylate cyclase by CO. Thus, we provide a model that explains enzyme activities of the nitrosyl and carboxy forms of the enzyme on the basis of a common mechanism.