Crystal structure of the complex between calyculin A and the catalytic subunit of protein phosphatase 1
Crystal structure of the complex between calyculin A and the catalytic subunit of protein phosphatase 1
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DOI：
10.1016/s0969-2126(02)00764-5
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发表时间：
2002-05-01
期刊：
影响因子：
5.7
通讯作者：
Miki, K
中科院分区：
文献类型：
--
作者：
Kita, A;Matsunaga, S;Miki, K
在2.0埃分辨率下测定了蛋白磷酸酶1（PP1）的催化亚基PP1 γ与海洋毒素calyculin A复合物的晶体结构。金属结合位点含有calyculin A的磷酸基团，并通过PP1和calyculin A之间的亲水相互作用形成紧密的网络。Calyculin A位于三个沟槽中的两个，即分子表面的疏水沟槽和酸性沟槽中。这是第一次观察到，该抑制剂采用的不是假环构象，而是延伸构象，以便与蛋白质形成复合物。calyculin A的氨基酸末端以有限的方式促进与PP1 γ的结合，这与剂量抑制分析研究的结果一致。
The crystal structure of the catalytic subunit of the protein phosphatase 1 (PP1), PP1gamma, in complex with a marine toxin, calyculin A, was determined at 2.0 Angstrom resolution. The metal binding site contains the phosphate group of calyculin A and forms a tight network via the hydrophilic interactions between PP1 and calyculin A. Calyculin A is located in two of the three grooves, namely, in the hydrophobic groove and the acidic groove on the molecular surface. This is the first observation to note that the inhibitor adopts not a pseuclocyclic conformation but an extended conformation in order to form a complex with the protein. The amino acid terminus of calyculin A contributes, in a limited manner, to the binding to PP1gamma, which is consistent with findings from the studies of dose-inhibition analysis.