The N-terminal segment of antithrombin acts as a steric gate for the binding of heparin

Protein Science : a Publication of the Protein Society
H L FittonR N Pike

Abstract

The binding of heparin causes a conformational change in antithrombin to give an increased heparin binding affinity and activate the inhibition of thrombin and factor Xa. The areas of antithrombin involved in binding heparin and stabilizing the interaction in the high-affinity form have been partially resolved through the study of both recombinant and natural variants. The role of a section of the N-terminal segment of antithrombin, residues 22-46 (segment 22-46), in heparin binding was investigated using rapid kinetic analysis of the protein cleaved at residues 29-30 by limited proteolysis with thermolysin. The cleaved antithrombin had 5.5-fold lowered affinity for heparin pentasaccharide and 1.8-fold for full-length, high-affinity heparin. It was shown that, although the initial binding of heparin is slightly enhanced by the cleavage, it dissociates much faster from the cleaved form, giving rise to the overall decrease in heparin affinity. This implies that the segment constituting residues 22-46 in the N terminus of antithrombin hinders access to the binding site for heparin, hence the increased initial binding for the cleaved form, whereas, when heparin is bound, segment 22-46 is involved in the stabilization of the binding...Continue Reading

References

Nov 1, 1978·The Biochemical Journal·T C LaurentU Lindahl
Oct 3, 1992·Biochimica Et Biophysica Acta·S DeLauderD H Atha
Jul 31, 1980·Biochemical and Biophysical Research Communications·L T Hunt, M O Dayhoff
Apr 15, 1994·Structure·R W CarrellM R Wardell
Mar 1, 1996·The Biochemical Journal·W S ChangR W Carrell
Feb 7, 1998·Proceedings of the National Academy of Sciences of the United States of America·L JinR W Carrell

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Citations

Jan 24, 2004·Bioorganic & Medicinal Chemistry·Gunnar T Gunnarsson, Umesh R Desai
Jul 5, 2012·Journal of Thrombosis and Haemostasis : JTH·I Martínez-MartínezJ Corral
Sep 1, 2000·Journal of Molecular Biology·J C WhisstockA M Lesk

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