Crystal structure of calcium bound domain VI of calpain at 1.9 Å resolution and its role in enzyme assembly, regulation, and inhibitor binding

Crystal structure of calcium bound domain VI of calpain at 1.9 Å resolution and its role in enzyme assembly, regulation, and inhibitor binding
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1.9 Å 分辨率下钙蛋白酶钙结合域 VI 的晶体结构及其在酶组装、调节和抑制剂结合中的作用

DOI:
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发表时间:
1997
期刊:
Nature Structural Biology
影响因子:
--
通讯作者:
S. Narayana
S. Narayana
中科院分区:
--
文献类型:
--
作者:
G. Lin;D. Chattopadhyay;M. Maki;K. Wang;M. Carson;Lei Jin;P. Yuen;E. Takano;M. Hatanaka;L. DeLucas;S. Narayana

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猪钙蛋白酶钙结合结构域 VI 的三维结构已确定为 1.9 Å 分辨率。晶体结构揭示了 5 个 EF 指针,比之前建议的多了一个。有两对 EF 手,一对 (EF1-EF2) 显示“开放”构象,另一对 (EF3-EF4) 显示“闭合”构象。不同寻常的是,在 EF4 钙结合环的 C 末端发现了一个钙原子。由于钙结合环中有两个额外的残基,第五个 EF 手 (EF5) 处于“闭合”构象。 EF5 与非晶体相关分子的相应第五个 EF 手配对。考虑到 EFS 在结构域 VI 的同二聚体形成中的作用,我们提出了异二聚钙蛋白酶组装的模型。 Ca2+ 结合域 VI 抑制剂 (PD150606) 复合物的晶体结构已细化至 2.1 Å 分辨率。讨论了钙蛋白酶抑制的可能模式。
The three dimensional structure of calcium-bound domain VI of porcine calpain has been determined to 1.9 Å resolution. The crystal structure reveals five EF-hands, one more than previously suggested. There are two EF-hand pairs, one pair (EF1-EF2) displays an ‘open’ conformation and the other (EF3-EF4) a ‘closed’ conformation. Unusually, a calcium atom is found at the C-terminal end of the calcium binding loop of EF4. With two additional residues in the calcium binding loop, the fifth EF-hand (EF5) is in a ‘closed’ conformation. EF5 pairs up with the corresponding fifth EF-hand of a non-crystallographically related molecule. Considering the EFS's role in a homodimer formation of domain VI, we suggest a model for the assembly of heterodimeric calpain. The crystal structure of a Ca2+ bound domain VI–inhibitor (PD150606) complex has been refined to 2.1 Å resolution. A possible mode for calpain inhibition is discussed.
钙蛋白酶亚基在催化过程中保持结合。
DOI: --
发表时间: 1996
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