Activity of Serpins in Context to Hydrophobic Interaction.

The activity of serpins uses a specific mechanism or process. This process comprises several steps and is related to significant structural changes that involve significant displacement of chain fragments and whole molecules of protease. An important role is played by a segment of the serpin chain called the Reactive Central Loop (RCL), which interacts with the protease by inhibiting its activity. For the covalent binding of the protease to serpin, the movement of the protease molecule is an effect of splicing the RCL segment into beta-sheet A of serpin. There are structural forms-native, latent, Michaelis complex (non-covalent enzyme-inhibitor complex prior to RCL cleavage), covalent serpin-protease complex, and cleaved-associated with serpin activity. In this work, all these structural forms are discussed using the fuzzy oil drop (FOD-M) model, where the assessment criterion of structuring is based on identifying the type of hydrophobicity distribution. The analysis reveals the specificity of the inhibition mechanism, including the specific action of the RCL. The structural changes involved in this process have been shown to preserve the distribution of hydrophobicity in the form preferred by the aqueous environment in which serpins are active. The disorder (according to FOD-M model) in two complexes (Michaelis and covalent) is hypothetically treated as code for degradation factors. The applied model assesses the function-related structures using the hydrophobicity distribution as the criterion in contrast to many publications based on energetic aspects of serpin activity. Structural changes appear appropriate for water environments-the environment of serpin activity.