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Structural basis for broad substrate specificity of earthworm fibrinolytic enzyme component A.

Authors
  • Wang, Chao
  • Wang, Feng
  • Li, Mei
  • Tang, Yong
  • Zhang, Ji-Ping
  • Gui, Lu-Lu
  • An, Xiao-Min
  • Chang, Wen-Rui
Type
Published Article
Journal
Biochemical and biophysical research communications
Publication Date
Dec 17, 2004
Volume
325
Issue
3
Pages
877–882
Identifiers
PMID: 15541372
Source
Medline
License
Unknown

Abstract

Earthworm fibrinolytic enzyme component A (EFE-a) possesses an S1 pocket, which is typical for an elastase-like enzyme, but it can still hydrolyze varieties of substrates, and it exhibits wide substrate specificity. Former structure studies suggested that the four-residue insertion after Val(217) might endow EFE-a with this specificity. Based on the native crystal structure at a resolution of 2.3A, we improved the native crystal structure to 1.8A and determined its complex structure with the inhibitor Meo-Suc-Ala-Ala-Pro-Val-CMK at a resolution of 1.9A. The final structures show that: (1) EFE-a possesses multisubstrate-binding sites interacting with the substrates; (2) significant conformation adjustment takes place at two loops binding to the N-terminal of the substrates, which may enhance the interaction between the enzyme and the substrates. These characteristics make the substrate-specificity of EFE-a less dependent on the property of its S1-pocket and may endow the enzyme with the ability to hydrolyze chymotrypsin-specific substrates and even trypsin-specific substrates.

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