Mechanisms of antithrombin polymerisation and heparin activation probed by the insertion of synthetic reactive loop peptides

Biol Chem. 1997 Sep;378(9):1059-63. doi: 10.1515/bchm.1997.378.9.1059.


Incubation of antithrombin with a series of synthetic reactive loop peptides showed that 6-mer and 7-mer peptides, P14-P9 and P14-P8 of antithrombin respectively, induced loop-sheet polymerisation and binary complex formation. These peptides are likely to anneal to the upper part of the dominant A-sheet, favouring sheet opening and allowing insertion of a second reactive loop in the lower part of the A-sheet to form polymers. The insertion of longer peptides filled the A-sheet beyond the P7 position and prevented polymerisation. Heparinised antithrombin was more resistant to polymerisation and peptide insertion, indicating that heparin induces a conformational change that closes the A-sheet and expels the reactive loop.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antithrombin III / chemistry*
  • Electrophoresis, Polyacrylamide Gel
  • Helix-Loop-Helix Motifs
  • Heparin / chemistry*
  • Hot Temperature
  • Molecular Weight
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Polymers
  • Protein Conformation
  • Serpins / chemistry


  • Peptides
  • Polymers
  • Serpins
  • Antithrombin III
  • Heparin