ATP analog specificity of cAMP-dependent protein kinase, cGMP-dependent protein kinase, and phosphorylase kinase.
ATP analog specificity of cAMP-dependent protein kinase, cGMP-dependent protein kinase, and phosphorylase kinase.
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DOI：
10.1111/j.1432-1033.1984.tb08100.x
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发表时间：
1984-04
期刊：
影响因子：
--
通讯作者：
D. Flockhart;W. Freist;J. Hoppe;T. Lincoln;J. Corbin
中科院分区：
文献类型：
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作者：
D. Flockhart;W. Freist;J. Hoppe;T. Lincoln;J. Corbin
通过比较27种类似物在蛋白激酶反应中与ATP竞争的能力，比较了同质cGMP依赖性蛋白激酶和cAMP依赖性蛋白激酶催化亚基的ATP类似物特异性。虽然这些数据表明两个同源的环状核苷酸依赖性蛋白激酶的ATP位点之间的一般相似性，特别是在腺嘌呤结合口袋的具体差异表示。亲和力的这些差异表明每个激酶的潜在有用的ATP类似物抑制剂。例如，经纯化的cAMP依赖性蛋白激酶的调节亚基的明显自磷酸化被三磷酸星云素阻断，表明磷酸化是由cGMP依赖性蛋白激酶的痕量污染催化的。还使用磷酸化酶B激酶测试了一些ATP类似物，以便将该酶与环核苷酸依赖性酶进行比较。所有三种蛋白激酶对ATP的嘌呤部分都具有高特异性，而对核糖或三磷酸的特异性较低。磷酸化酶B激酶的ATP位点与环核苷酸依赖性蛋白激酶的ATP位点之间的相似性表明它与它们相关。在这项研究中检查的酶的ATP类似物的特异性是不同的几个无关的ATP利用酶的报道。
The ATP analog specificities of the homogeneous cGMP-dependent protein kinase and the catalytic subunit of cAMP-dependent protein kinase have been compared by the ability of 27 analogs to compete with ATP in the protein kinase reaction. Although the data suggest general similarities between the ATP sites of the two homologous cyclic-nucleotide-dependent protein kinases, specific differences especially in the adenine binding pocket are indicated. These differences in affinity suggest potentially useful ATP analog inhibitors of each kinase. For example, apparent autophosphorylation of the purified regulatory subunit of the cAMP-dependent protein kinase is blocked by nebularin triphosphate, suggesting that the phosphorylation is catalyzed by trace contamination of cGMP-dependent protein kinase. Some of the ATP analogs have also been tested using phosphorylase b kinase in order to compare this enzyme with the cyclic-nucleotide-dependent enzymes. All three protein kinases have high specificity for the purine moiety of ATP, and lower specificity for the ribose or triphosphate. The similarity between the ATP site of phosphorylase b kinase to that of the cyclic-nucleotide-dependent protein kinases suggests that it is related to them. The ATP analog specificities of enzymes examined in this study are different from those reported for several unrelated ATP-utilizing enzymes.