The intact and cleaved human antithrombin III complex as a model for serpin-proteinase interactions

Nat Struct Biol. 1994 Jan;1(1):48-54. doi: 10.1038/nsb0194-48.


Antithrombin is a member of the serine proteinase inhibitor (serpin) family which contain a flexible reactive site loop that interacts with, and is cleaved by the target proteinase. In cleaved and latent serpins, the reactive site loop is inserted into a large central beta-sheet in the same molecule, whereas in ovalbumin, a nonfunctional serpin, the reactive site loop is completely exposed and in an alpha-helical conformation. However, in neither conformation can the reactive site loop bind to target proteinases. Here we report the structure of an intact and cleaved human antithrombin complex. The intact reactive site loop is in a novel conformation that seems well suited for interaction with proteinases such as thrombin and blood coagulation factor Xa.

MeSH terms

  • Amino Acid Chloromethyl Ketones / chemistry
  • Amino Acid Chloromethyl Ketones / metabolism
  • Amino Acid Sequence
  • Antithrombin III / chemistry*
  • Antithrombin III / genetics
  • Antithrombin III / metabolism
  • Binding Sites
  • Electrochemistry
  • Endopeptidases / chemistry*
  • Endopeptidases / metabolism
  • Humans
  • In Vitro Techniques
  • Models, Molecular
  • Molecular Sequence Data
  • Ovalbumin / chemistry
  • Ovalbumin / metabolism
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Secondary
  • Serpins / chemistry*
  • Serpins / metabolism
  • Thrombin / chemistry
  • Thrombin / metabolism


  • Amino Acid Chloromethyl Ketones
  • Serpins
  • Antithrombin III
  • Ovalbumin
  • Endopeptidases
  • Thrombin
  • phenylalanyl-prolyl-arginine-chloromethyl ketone