Kita Akiko, Matsunaga Shigeki, Takai Akira, Kataiwa Hirotaka, Wakimoto Toshiyuki, Fusetani Nobuhiro, Isobe Minoru, Miki Kunio
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
Structure. 2002 May;10(5):715-24. doi: 10.1016/s0969-2126(02)00764-5.
The crystal structure of the catalytic subunit of the protein phosphatase 1 (PP1), PP1 gamma, in complex with a marine toxin, calyculin A, was determined at 2.0 A 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 pseudocyclic 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 PP1 gamma, which is consistent with findings from the studies of dose-inhibition analysis.
测定了蛋白磷酸酶1（PP1）催化亚基PP1γ与一种海洋毒素——花萼海绵诱癌毒素A（calyculin A）复合物的晶体结构，分辨率为2.0埃。金属结合位点包含花萼海绵诱癌毒素A的磷酸基团，并通过PP1与花萼海绵诱癌毒素A之间的亲水相互作用形成紧密网络。花萼海绵诱癌毒素A位于分子表面三个凹槽中的两个，即疏水凹槽和酸性凹槽。这是首次观察到该抑制剂为了与蛋白质形成复合物而不是采用假环构象，而是采用伸展构象。花萼海绵诱癌毒素A的氨基酸末端对与PP1γ的结合贡献有限，这与剂量抑制分析研究的结果一致。
