Weber I T, Steitz T A, Bubis J, Taylor S S
Biochemistry. 1987 Jan 27;26(2):343-51. doi: 10.1021/bi00376a003.
The mammalian cAMP-dependent protein kinases have regulatory (R) subunits that show substantial homology in amino acid sequence with the catabolite gene activator protein (CAP), a cAMP-dependent gene regulatory protein from Escherichia coli. Each R subunit has two in-tandem cAMP binding domains, and the structure of each of these domains has been modeled by analogy with the crystal structure of CAP. Both the type I and II regulatory subunits have been considered, so that four cAMP binding domains have been modeled. The binding of cAMP in general is analogous in all the structures and has been correlated with previous results based on photolabeling and binding of cAMP analogues. The model predicts that the first cAMP binding domain correlates with the previously defined fast dissociation site, which preferentially binds N6-substituted analogues of cAMP. The second domain corresponds to the slow dissociation site, which has a preference for C8-substituted analogues. The model also is consistent with cAMP binding in the syn conformation in both sites. Finally, this model has targeted specific regions that are likely to be involved in interdomain contacts. This includes contacts between the two cAMP binding domains as well as contacts with the amino-terminal region of the R subunit and with the catalytic subunit.
哺乳动物的环磷酸腺苷（cAMP）依赖性蛋白激酶具有调节（R）亚基，这些亚基在氨基酸序列上与来自大肠杆菌的cAMP依赖性基因调节蛋白——分解代谢基因激活蛋白（CAP）具有高度同源性。每个R亚基有两个串联的cAMP结合结构域，并且这些结构域中的每一个的结构都已通过与CAP的晶体结构类比进行了建模。I型和II型调节亚基都已被考虑在内，因此已对四个cAMP结合结构域进行了建模。一般来说，cAMP在所有结构中的结合都是类似的，并且已与基于光标记和cAMP类似物结合的先前结果相关联。该模型预测，第一个cAMP结合结构域与先前定义的快速解离位点相关，该位点优先结合cAMP的N6-取代类似物。第二个结构域对应于缓慢解离位点，其偏好C8-取代类似物。该模型也与两个位点中cAMP以顺式构象结合一致。最后，该模型确定了可能参与结构域间接触的特定区域。这包括两个cAMP结合结构域之间的接触以及与R亚基的氨基末端区域和催化亚基的接触。
