Crystal structure of plasma kallikrein reveals the unusual flexibility of the S1 pocket triggered by Glu217
Crystal structure of plasma kallikrein reveals the unusual flexibility of the S1 pocket triggered by Glu217
复制标题
血浆激肽释放酶的晶体结构揭示了 Glu217 触发的 S1 口袋异常的灵活性
DOI：
10.1002/1873-3468.13191
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发表时间：
2018
期刊：
影响因子：
3.5
通讯作者：
Huang M. D.
中科院分区：
文献类型：
--
作者：
Xu M. M;Chen Y. Y;Xu P;Andreasen P. A;Jiang L. G;Li J. Y;Huang M. D.
丝氨酸蛋白酶在许多生理和病理生理过程中发挥重要作用。此外，丝氨酸蛋白酶是研究酶的催化和抑制机制的经典对象。在这里，我们确定了丝氨酸蛋白酶，鼠血浆激肽释放酶（mPK），其与肽抑制剂的复合物的晶体结构。尽管复合物中的mPK采用典型的蛋白酶结构，但apo-mPK显示出以前未观察到的结构功能：完整S1口袋的入口被Glu 217阻断。此外，分子动力学模拟和功能测定支持Glu 217的灵活性，并表明这种灵活性在调节丝氨酸蛋白酶的活性中起作用。
Serine proteases play important roles in numerous physiological and pathophysiological processes. Moreover, serine proteases are classical subjects for studies of catalytic and inhibitory mechanisms of enzymes. Here, we determined the crystal structures of a serine protease, murine plasma kallikrein (mPK), and its complex with a peptidic inhibitor. Although mPK in the complex adopts a canonical protease structure, the apo‐mPK exhibits a previously unobserved structural feature: the entrance of the intact S1 pocket is blocked by Glu217. In addition, molecular dynamics simulations and functional assays support the flexibility of Glu217 and suggest that this flexibility plays a role in regulating the activity of serine proteases.