Serine Protease Inhibitors - Structure

Structure

Structural biology has played a central role in the understanding of serpin function and biology. Over eighty serpin structures, in a variety of different conformations (described below), have been determined to date. Although the function of serpins varies widely, these molecules all share a common structure (or fold).

The structure of the non-inhibitory serpin ovalbumin, and the inhibitory serpin antitrypsin, revealed the archetype native serpin fold. All typically have three β-sheets (termed A, B and C) and eight or nine α-helices (hA-hI) (see figure 4). Serpins also possess an exposed region termed the reactive centre loop (RCL) that, in inhibitory molecules, includes the specificity determining region and forms the initial interaction with the target protease. In antitrypsin, the RCL is held at the top of the molecule and is not pre-inserted into the A β-sheet (figure 4, left panel). This conformation commonly exists in dynamic equilibrium with a partially inserted native conformation seen in other inhibitory serpins (see figure 4, right panel).