一氧化碳激活鸟苷酸环化酶的基础。
Basis of guanylate cyclase activation by carbon monoxide.
作者信息
Kharitonov V G, Sharma V S, Pilz R B, Magde D, Koesling D
机构信息
Department of Medicine, University of California, San Diego, La Jolla 92093-0652, USA.
出版信息
Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2568-71. doi: 10.1073/pnas.92.7.2568.
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 six-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.
通过闪光光解在pH 7.5条件下研究了一氧化碳与鸟苷酸环化酶[GTP焦磷酸裂解酶（环化），EC 4.6.1.2]的结合动力学以及一氧化碳从羧基鸟苷酸环化酶上的解离动力学，在23℃下得到的速率常数分别为1.2±0.1×10⁵ M⁻¹·s⁻¹和28±2 s⁻¹。虽然一氧化碳的结合速率常数与血红蛋白的T态相同，但一氧化碳的解离速率常数比六配位羧基血红素蛋白预期的要高得多；然而吸收光谱表明是六配位血红素。这两个观察结果通过一种反应机制得到调和，即一氧化碳的解离通过一个五配位中间体进行。这个中间体在结构上与鸟苷酸环化酶的五配位亚硝酰血红素衍生物非常相似，可能是观察到的一氧化碳对鸟苷酸环化酶4倍激活作用的原因。因此，我们提供了一个模型，基于一个共同机制解释该酶亚硝酰和羧基形式的酶活性。
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