Expression, purification and molecular modeling of recombinant fibrinogenase [IV], a metalloproteinase from Deinakistrodon acutus venom

Toxicon. 2006 Feb;47(2):241-8. doi: 10.1016/j.toxicon.2005.11.005. Epub 2005 Dec 28.

Abstract

A novel metalloproteinase, recombinant fibrinogenase IV (rFIV(a)), was expressed and purified from Deinakistrodon acutus venom. It was a single chain protein with an apparent molecular weight 27 kDa and an isoeletric point of pH 7.1. RFIV(a) cleaved preferentially the Aalpha-chain and also cleaved Bbeta, gamma-chains of fibrinogen when the incubation time was prolonged. The proteolytic activity was inhibited by EDTA, l-cysteine, and DTT, indicating rFIV(a) was a metalloproteinase requiring disulfide bonds for its activity. It kept above 85% of the initial activity from pH 4.5-11, showed an equal maximum activity at the temperature range from 30 to 50 degrees C, and was inactivated by Zn2+, Cu2+ and Cd2+. Homology modeling of rFIV(a) showed that two highly conserved disulfide bonds (Cys159-Cys164 and Cys117-Cys197) was maintained from its structure, and it exhibited the characteristic conserved motif H142E143XXH146XXGXXH152, whose three histidine residues were involved in binding of the catalytically essential zinc ion. This work demonstrates the expression, purification and characterization of recombinant fibrinogenase IV, which belongs to class P-I metalloproteinase from D. acutus venom.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Enzyme Stability
  • Fibrinogen / metabolism*
  • Gene Expression
  • Hydrogen-Ion Concentration
  • Metalloproteases / chemistry*
  • Metalloproteases / isolation & purification*
  • Metalloproteases / metabolism
  • Models, Molecular*
  • Protein Conformation
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Snake Venoms / enzymology*
  • Snakes*
  • Temperature

Substances

  • Snake Venoms
  • Fibrinogen
  • Metalloproteases