Question

task

Another factor that participates in the coagulation cascade is factor XIa. Like other proteases in the blood, factor XIa is regulated by an inhibitor, antithrombin III, which is a member of the serine protease inhibitor family (serpins).
1. Why does the body need an inhibitor like antithrombin?

Heparin is a highly sulfated glycosaminoglycan polymer that affects the activity of serpins like antithrombin III. It is used in medicine to treat inter alia thrombosis (formation of blood clots in the blood) and as an additive to donor blood, to counteract coagulation during storage. The chemical structure of a heparin unit is shown below.

CH2OSO3 cOO он ÖSO3 NHSO3 Heparin

2. Which group of substances belong to heparin and what functional groups contain it?
The figure below shows the results of an experiment in which the effect of antithrombin III on factor XIa's proteolytic function was measured, with and without heparin present.

The effect of antithrombin III (x-axis, μM) on factor XIa's proteolytic activity (at 8 nM) is indicated along the y-axis of arbitrary units in the presence as well as without heparin (0.28 μM).
Heparin binds to an XBBXBX consensus motif in the protease, where X is an uncharged and B is a basic amino acid residue.
3. Explain how heparin interacts with the consensus motif.

4. Suggest how heparin affects the interaction between serpine and protease?

Answer 1