Antithrombin and heparin.
Antithrombin, the main inhibitor of thrombosis in blood, is bound and activated by the heparin-like side-chains that line the small vasculature. We now have good depictions of the heparin-binding site on antithrombin, and of the way in which mutations at this site cause thrombotic disease. The interaction of heparin with antithrombin is, however, a kinetic one, with binding being followed by formation of a complex with thrombin and then release from the heparin. Our understanding of the processes involved is currently based on crystallographic models but, for a mobile mechanism, these merely provide snapshots - what is needed is a movie.
Carrell
R
R
Department of Haematology, University of Cambridge, MRC Centre, Hills Road, Cambridge, UK.
Skinner
R
R
Warden
M
M
Whisstock
J
J
D000818:Animals; D000991:Antithrombins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D006493:Heparin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D013927:Thrombosis / Q000235:genetics / Q000378:metabolism
D000991:Antithrombins; D006493:Heparin