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Crystal structure of plasma kallikrein reveals the unusual flexibility of the S1 pocket triggered by Glu217
Author(s) -
Xu Mingming,
Chen Yayu,
Xu Peng,
Andreasen Peter A.,
Jiang Longguang,
Li Jinyu,
Huang Mingdong
Publication year - 2018
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13191
Subject(s) - proteases , kallikrein , serine , serine protease , flexibility (engineering) , protease , chemistry , enzyme , biochemistry , statistics , mathematics
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. Enzymes EC: 3.4.21.34