Contribution of allosteric disulfide bonds to regulation of hemostasis.

Protein disulfide bonds are covalent links between pairs of Cys residues in the polypeptide chain. Acquisition of disulfide bonds is an important way that proteins have evolved and are continuing to evolve. These bonds serve either a structural or functional role. There are two types of functional disulfide: the catalytic bonds that reside in the active sites of oxidoreductases and the allosteric bonds. Allosteric disulfides are defined as bonds that have evolved to control the manner in which proteins function by breaking or forming in a precise way. The known allosteric bonds have a particular configuration known as the -RHStaple. Several hemostasis proteins contain -RHStaple disulfides and there is increasing evidence that some of these bonds may be involved in the functioning of the protein in which they reside. The best studied of these to date is the -RHStaple disulfide in tissue factor and its role in de-encryption of the cofactor.