THE ROLE OF CONFORMATIONAL CHANGE IN SERPIN STRUCTURE AND FUNCTION

Serpins are members of a family of structurally related protein inhibi tors of serine proteinases, with molecular masses between 40 and 100kD a. In contrast to other, simpler, proteinase inhibitors, they may inte ract with proteinases as inhibitors, as substrates, or as both. They u ndergo conformational interconversions upon complex formation with pro teinase, upon binding of some members to heparin, upon proteolytic cle avage at the reactive center, and under mild denaturing conditions. Th ese conformational changes appear to be critical in determining the pr operties of the serpin. The structures and stabilities of these variou s forms may differ significantly. Although the detailed structural cha nges required for inhibition of proteinase have yet to be worked out, it is clear that the serpin does undergo a major conformational change . This is in contrast to other, simpler, families of protein inhibitor s of serine proteinases, which bind in a substrate-like or product-lik e manner. Proteolytic cleavage of the serpin can result in a much more stable protein with new biological properties such as chemo-attractan t behaviour. These structural transformations in serpins provide oppor tunities for regulation of the activity and properties of the inhibito r and are likely be important in vivo, where serpins are involved in b lood coagulation, fibrinolysis, complement activation and inflammation .