Activation of soluble guanylate cyclase by carbon monoxide and nitric oxide: a mechanistic model.
Activation of soluble guanylate cyclase by carbon monoxide and nitric oxide: a mechanistic model.
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一氧化碳和一氧化氮激活可溶性鸟苷酸环化酶：机械模型。
作者：
V. Sharma;D. Magde
来自牛肺的可溶性鸟苷酸环化酶 (GC) 被一氧化碳 (CO) 激活 4 倍，被一氧化氮 (NO) 激活 400 倍。总结了 CO 和 NO 与 GC 连接的光谱和动力学数据，并与肌红蛋白 (Mb)、血红蛋白 (Hb) 和血红素模型化合物的类似数据进行了比较。动力学、热力学和结构数据构成了构建模型的基础，以了解两种配体影响血红素附近的蛋白质结构的方式（对于一般血红素蛋白，特别是对于GC）。最重要的数据是，尽管配体与 GC 的结合率与 Mb 和 Hb 的结合率相似，但它们的解离率要快得多。这表明 NO 和 CO 复合物中五配位和六配位血红素铁之间存在微妙的平衡。基于这些和其他数据，提出了 GC 激活模型：第一步是形成六配位物种，伴随蛋白质结构的三级和四级结构变化以及酶活性约 4 倍的增加。第二步，适用于 NO，铁与近端组氨酸的键断裂，导致四级和三级结构进一步松弛，活性进一步增加 100 倍。这是激活过程中的主要事件，可用于 NO 和可能的其他激活剂或激活剂组合。最后，有人提出，步骤 2 中释放的近端碱基，或由于连接后结构变化而适当定位的一些其他蛋白质碱基，可以提供催化 GTP --> cGMP 反应的亲核取代中心。提供了衍生化原血红素模型化合物中类似反应的示例。该反应机制试图在共同的基础上合理化GC、血红素缺陷GC、GC-CO和GC-NO的相对酶活性，并对未来可能发现的新激活剂做出预测。
Soluble guanylate cyclase (GC) from bovine lung is activated 4-fold by carbon monoxide (CO) and 400-fold by nitric oxide (NO). Spectroscopic and kinetic data for ligation of CO and NO with GC are summarized and compared with similar data for myoglobin (Mb), hemoglobin (Hb), and heme model compounds. Kinetic, thermodynamic, and structural data form a basis on which to construct a model for the manner in which the two ligands affect protein structure near the heme for heme proteins in general and for GC in particular. The most significant datum is that although association rates of ligands with GC are similar to those with Mb and Hb, their dissociation rates are dramatically faster. This suggests a delicate balance between five- and six-coordinate heme iron in both NO and CO complexes. Based on these and other data, a model for GC activation is proposed: The first step is formation of a six-coordinate species concomitant with tertiary and quaternary structural changes in protein structure and about a 4-fold increase in enzyme activity. In the second step, applicable to NO, the bond from iron to the proximal histidine ruptures, leading to additional relaxation in the quaternary and tertiary structure and a further 100-fold increase in activity. This is the main event in activation, available to NO and possibly other activators or combinations of activators. It is proposed, finally, that the proximal base freed in step 2, or some other protein base suitably positioned as a result of structural changes following ligation, may provide a center for nucleophilic substitution catalyzing the reaction GTP --> cGMP. An example is provided for a similar reaction in a derivatized protoheme model compound. The reaction mechanism attempts to rationalize the relative enzymatic activities of GC, heme-deficient GC, GC-CO, and GC-NO on a common basis and makes predictions for new activators that may be discovered in the future.
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影响因子：
2.9
作者：
G. Deinum;J. R. Stone;Gerald T. Babcock;M. Marletta
通讯作者：
G. Deinum;J. R. Stone;Gerald T. Babcock;M. Marletta
DOI：
--
发表时间：
1986-04
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
L. Ignarro;J. Adams;P. M. Horwitz;K. S. Wood
通讯作者：
L. Ignarro;J. Adams;P. M. Horwitz;K. S. Wood
DOI：
10.1006/bbrc.1997.7470
发表时间：
1997-10-09
影响因子：
3.1
作者：
Kharitonov, VG;Russwurm, M;Koesling, D
通讯作者：
Koesling, D
DOI：
10.1073/pnas.92.7.2568
发表时间：
1995-03-28
影响因子：
11.1
作者：
KHARITONOV, VG;SHARMA, VS;KOESLING, D
通讯作者：
KOESLING, D
影响因子：
2.9
作者：
DUPRAT, AF;TRAYLOR, TG;MAGDE, D
通讯作者：
MAGDE, D