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

Hazel L. Fitton, Robert N. Pike, Robin W. Carrell, Wun Shaing W. Chang

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49 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1059-1063
Number of pages5
JournalBiological Chemistry
Volume378
Issue number9
Publication statusPublished - 1 Sep 1997
Externally publishedYes

Keywords

  • Antithrombin
  • Heparin
  • Pentasaccharide
  • Peptide
  • Polymerisation
  • Serpin

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