Predicted structures of cAMP binding domains of type I and II regulatory subunits of cAMP-dependent protein kinase.
Predicted structures of cAMP binding domains of type I and II regulatory subunits of cAMP-dependent protein kinase.
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cAMP 依赖性蛋白激酶 I 型和 II 型调节亚基的 cAMP 结合域的预测结构。
DOI：
10.1021/bi00376a003
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发表时间：
1987
期刊：
影响因子：
2.9
通讯作者：
Taylor,SS
中科院分区：
文献类型：
--
作者：
Weber,IT;Steitz,TA;Bubis,J;Taylor,SS
加州大学化学系，圣地亚哥，拉霍亚，加利福尼亚州 92093 收稿日期：1986 年 6 月 24 日；修订稿于 1986 年 9 月 18 日收到摘要：哺乳动物 cAMP 依赖性蛋白激酶具有调节 (R) 亚基，其氨基酸序列与分解代谢物基因激活蛋白 (CAP)（一种来自大肠杆菌的 cAMP 依赖性基因调节蛋白）具有显着同源性。每个 R 亚基都有两个串联的 cAMP 结合域，每个域的结构均通过与 CAP 晶体结构的类比进行建模。 I 型和 II 型调节亚基都已被考虑，因此四个 cAMP 结合域已被建模。 cAMP 的结合总体上在所有结构中都是类似的，并且与之前基于 cAMP 类似物的光标记和结合的结果相关。该模型预测第一个 cAMP 结合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慢解离位点，该位点优先选择 C8 取代的类似物。该模型也与两个位点的顺式构象中的 cAMP 结合一致。最后，该模型针对可能涉及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 亚基氨基末端区域和催化亚基的接触。（环状 AMP 在原核和真核细胞中都起着重要的调节作用。大肠杆菌分解代谢基因激活蛋白 (CAP) 感知 cAMP 的水平，并在 cAMP 存在的情况下调节多个操纵子的转录（Zubay 等人，1970；Anderson 等人） CAP 在 cAMP 存在的情况下与特定 DNA 序列结合，并调节包括乳糖、半乳糖和 ara C 在内的几种操纵子的转录 [参见 deCrombrugghe 等人 (1984) 以及 deCrombrugghe 和 Pastan (1978)]。 具有两个结合的 cAMP 分子的 CAP 二聚体的晶体结构已被确定（McKay 和 Steitz，1981；麦凯
Department of Chemistry, University of California, San Diego, LaJolla, California 92093 Received June 24, 1986; Revised Manuscript Received September 18, 1986 abstract: 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 modeledby analogy with the crystal structure of CAP. Boththe type I and II regulatory subunits have been considered, so that four cAMP binding domains have been modeled. Thebinding ofcAMP 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.(Cyclic AMP plays an important regulatory role in both prokaryotic and eukaryotic cells. The Escherichia coli cata-bolite gene activator protein (CAP) senses the level of cAMP and regulates transcriptionfrom several operons in the presence of cAMP (Zubay et al., 1970; Anderson et al., 1972). CAP binds to specific DNA sequences in the presence of cAMP and regulates transcription of several operons including lactose, galactose, and ara C [for review, see deCrombrugghe et al.(1984) and deCrombrugghe and Pastan (1978)]. The crystal structure of the CAP dimer with two bound molecules of cAMP has been determined (McKay & Steitz, 1981; McKay