钙蛋白酶结构域VI与钙结合的晶体结构，分辨率为1.9埃，及其在酶组装、调节和抑制剂结合中的作用。

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

作者信息

Lin G D, Chattopadhyay D, Maki M, Wang K K, Carson M, Jin L, Yuen P W, Takano E, Hatanaka M, DeLucas L J, Narayana S V

机构信息

Center for Macromolecular Crystallography, University of Alabama at Birmingham 35294, USA.

出版信息

Nat Struct Biol. 1997 Jul;4(7):539-47. doi: 10.1038/nsb0797-539.

DOI:10.1038/nsb0797-539

PMID:9228946

Abstract

The three dimensional structure of calcium-bound domain VI of porcine calpain has been determined to 1.9 A 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 EF5'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 A resolution. A possible mode for calpain inhibition is discussed.

摘要

猪钙蛋白酶与钙结合的结构域VI的三维结构已确定，分辨率为1.9埃。晶体结构显示有五个EF手结构，比之前认为的多一个。有两对EF手结构，一对（EF1-EF2）呈“开放”构象，另一对（EF3-EF4）呈“闭合”构象。不同寻常的是，在EF4的钙结合环的C末端发现一个钙原子。由于钙结合环中有另外两个残基，第五个EF手结构（EF5）呈“闭合”构象。EF5与一个非晶体学相关分子的相应第五个EF手结构配对。考虑到EF5在结构域VI同型二聚体形成中的作用，我们提出了一个异源二聚体钙蛋白酶组装的模型。与Ca2+结合的结构域VI-抑制剂（PD150606）复合物的晶体结构已精修至2.1埃分辨率。讨论了钙蛋白酶抑制的一种可能模式。