Allosteric Regulation of the Blood Clotting Cascade

Abstract

Recognition of functional partners is a pivotal factor in the regulation of protein interactions. The areas of direct contact between complementary molecules that interact according to Koshland’s "key - lock" scheme deserve special attention. The relevance of the study of this kind of interactions is obvious. In the case of the simplest serine proteinases the increased affinity of the enzyme to a certain area of the target protein is ensured by the synchronous interaction of the binding and allosteric sub-sites with amino acid residues of the target protein, that are adequate by ligand specificity and placed in an optimal conformation. The purpose of this work is to clarify the compliance of the components of the blood clotting cascade with this rule. Comparison of the primary sequences of sites of activation cleavage, reactive centers of serpins and sites of proteolytic inactivation testifies in favor of this assumption.

Strategies for surface coatings of implantable cardiac medical devices

“…All the events mentioned above address to inflammatory response and activation of the coagulation cascade. These conformation changes lead to the activation of coagulation factor XII and activate the intrinsic pathway of the coagulation cascade ( Schenone et al, 2004 ; Chen et al, 2007 ; Vogler and Siedlecki, 2009 ; Golas et al, 2010 ; Chernyshenko et al, 2022 ). Afterward, platelets respond to several external stimuli (e.g., thrombin from the coagulation cascade, adenosine diphosphate released from destroyed cells, and shear force) ( Schenone et al, 2004 ; Chernyshenko et al, 2022 ).…”

“…These conformation changes lead to the activation of coagulation factor XII and activate the intrinsic pathway of the coagulation cascade ( Schenone et al, 2004 ; Chen et al, 2007 ; Vogler and Siedlecki, 2009 ; Golas et al, 2010 ; Chernyshenko et al, 2022 ). Afterward, platelets respond to several external stimuli (e.g., thrombin from the coagulation cascade, adenosine diphosphate released from destroyed cells, and shear force) ( Schenone et al, 2004 ; Chernyshenko et al, 2022 ). These external events stimuli conduct the adhesion, activation, and aggregation of platelets at any thrombogenic surface ( Mackman, 2008 ; Freitas et al, 2010 ).…”

Serpins’ Reactive Sites Loops Mobility and Its Functional Value

“…Reactive centers of inhibitors of plasminogen activators of type I and type 2 contain alanine and glycine residues in P 2 '-positions (R 346 ↓M 347 A 348 and R 381 ↓T 382 G 383 , respectively). At the same time, according to the specificity of action, both tissue plasminogen activator and urokinase-like one are fully subject to the S 1 -S 2 '-rule [48], cleaving the activation site of plasminogen at the bond R 561 ↓V 562 V 563 (Fig. 6).…”