Allosteric Site of Serine Proteinases: Localization, Functional Role and Manifestations in Vitro

Abstract

The study of molecular mechanisms of regulation of biologically active molecules is a necessary condition for understanding the course of the processes mediated by them. Serine proteinases are a large group of enzymes that play a leading role in the regulation of numerous physiological and pathogenic processes. Like many enzymes, SP are allosteric ones. In addition to the active center, they contain the region, whose interaction with corresponding compound changes the activity of enzyme. Various compounds can act as allosteric effectors. They may be substrates, substrate-like compounds, and mimics of some fragments of substrates. Taking into account the importance of serine proteases’ functions, it’s deserve attention the systematic data on localization, functional role and manifestations of allosteric region.

Serpins’ Reactive Sites Loops Mobility and Its Functional Value

“…This is due to the violation of the condition critical for ensuring high affinity between the proteinase and the functionally determined bond. It consists in the synchronicity of the interaction of the binding S 1 and allosteric S 2 ' sub-sites of the enzyme with P 1 -and P 2 '-amino acid residues of the inhibitor placed in the proper conformation and corresponding to the ligand specificity [16]. For trypsin-like proteinases the ligand specificity of the allosteric site corresponds to positively charged and hydrophobic amino acid residues, and a decrease in the hydrophobicity of the substituent leads to a decrease in inhibitory properties, while a negatively charged substituent has no inhibitory properties [17].…”

Allosteric Regulation of the Blood Clotting Cascade

“…Activated enzymes can be activators of other pro-forms, forming a kind of activation cascades. In the case of the simplest seine proteinases the recognition and selective cleavage in protein pro-forms is a consequence of the synchronous interaction of the binding and allosteric sub-siyes of the enzyme with the corresponding residues of the activation cleavage region of the protein pro-form [1]. According to the Schechter-Berger nomenclature, the binding and allosteric sub-sites of the active center correspond to the S1-and S2'-sites of the zone of direct contact of the enzyme and the corresponding amino acid residues correspond to the P1-and P2'-residues, respectively (Fig.…”

“…Similarly, high affinity of the simplest serine proteins to the reactive centers of protein inhibitors of proteinases is ensured [1]. In terms of ligand specificity, the positively charged amino acid residues of lysine and arginine correspond to the binding site of trypsin (E.C.…”