Virtuelle (Nano) Welten: PDB Molecule of the Month 25: Thrombin

In the Right Place at the Right Time

Of course, blood clotting must be carefully regulated, otherwise the blood would be clotting in all of the wrong places. Errors in blood clotting have disastrous effects: improper blood clots in the heart can cause heart attacks and misplaced blood clots in the brain cause strokes. Thrombin is controlled in two ways. First, it is built as an inactive precursor, shown here at the bottom (two PDB files are used, 1a0h on the left and 2pf2--the little dotted line shows the piece that is missing). The inactive form has several extra domains, colored light blue here, that are clipped off when the protein is activated. The purple atoms at right-bottom are calcium ions, bound to specially modified glutamate amino acids. The strong positive charge on these ions tether the protein to the surfaces of blood vessels, so that thrombin stays put. Since thrombin is not free to spread, blood clots, once they start, will not spread everywhere. Only the thrombin right next to damage will be activated. Second, once thrombin is activated, as in the upper structure shown here (PDB entry 1ppb), it lasts only seconds, also limiting the clot to area of damage.

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