Crystal structure of the proenzyme domain of plasminogen
Crystal structure of the proenzyme domain of plasminogen
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DOI：
10.1021/bi991130r
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发表时间：
1999-08-24
期刊：
影响因子：
2.9
通讯作者：
Ringe, D
中科院分区：
文献类型：
--
作者：
Peisach, E;Wang, JY;Ringe, D
我们已经解决了纤溶酶原催化结构域前酶形式的X射线晶体结构，带有非本质突变M585Q、V673M和M788L，分辨率为2.0埃。该结构呈现一种失活的蛋白酶，其特征是Asp740(凝乳酶原194)氢键连接到His586(凝乳酶原40)，防止氧阴离子空穴和SI专一性口袋的正确形成。此外，催化三联体残基相对于糜蛋白酶家族中丝氨酸蛋白酶采用的活性构象是错位的。最后，观察到了一种独特的酶原失活形式，其特征是“嘴中之脚”机制，即Trp761(糜蛋白酶原215)被折叠到S1特异性口袋中，防止底物结合。
We have solved the X-ray crystal structure of the proenzyme form of the catalytic domain of plasminogen, with the nonessential mutations M585Q, V673M, and M788L, to 2.0 Angstrom resolution. The structure presents an inactive protease characterized by Asp740 (chymotrypsinogen 194) hydrogen bonded to His586 (chymotrypsinogen 40), preventing proper formation of the oxyanion hole and SI specificity pocket. In addition, the catalytic triad residues are misplaced relative to the active conformation adopted by serine proteases in the chymotrypsin family. Finally, a unique form of zymogen inactivation is observed, characterized by a "foot-in-mouth" mechanism in which Trp761 (chymotrypsinogen 215) is folded into the S1 specificity pocket preventing substrate binding.