Crystal structure of plasma kallikrein reveals the unusual flexibility of the S1 pocket triggered by Glu217

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DOI

  • Mingming Xu, Fuzhou University, State Key Laboratory of Structural Chemistry, Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences
  • ,
  • Yayu Chen, Fuzhou University
  • ,
  • Peng Xu, State Key Laboratory of Structural Chemistry, Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences
  • ,
  • Peter A. Andreasen
  • ,
  • Longguang Jiang, Fuzhou University
  • ,
  • Jinyu Li, Fuzhou University
  • ,
  • Mingdong Huang, Fuzhou University, State Key Laboratory of Structural Chemistry, Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences

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.

Original languageEnglish
JournalFEBS Letters
Volume592
Issue15
Pages (from-to)2658-2667
Number of pages10
ISSN0014-5793
DOIs
Publication statusPublished - Aug 2018

    Research areas

  • flexibility, molecular dynamics, plasma kallikrein, serine proteases, X-ray crystallography

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