Clotting factors: Clinical biochemistry and their roles as plasma enzymes

What We Know About Kininogen Structure – Importance for Function and Perspectives from Cryo-EM

“…The human High Molecular Weight Kininogen (HK) is a six domain glycoprotein with molecular weight of 108-120 kDa [1][2][3][4]. Distinct domains of mature HK can be listed Some features and functions are recognized for them.…”

“…The cleavage of HK in the smallest Domain 4 by activated plasma kallikrein (PK) releases nonapeptide bradykinin (RPPGFSPFR). Bradykinin (BK) boosts vasodilation and vascular permeability and can develop soft tissue swelling (angioedema) [4]. Domains 5 and 6 are vital for the contact (intrinsic) pathway of blood coagulation.…”

“…Human HK can be divided into a heavy and a light chain after proteolytic cleavage in Domain 4 and reduction of disulfide bridge. The heavy chain spreads between amino acid residues 1-362 and contains domains 1-3 and the first six amino acids of the short Domain -Lysyl-Bradykinin (LBK) which is subsequently split to BK by the enzyme arginine aminopeptidase [4].…”

“…Kininogens or Fitzgerald factors are multidomain glycoproteins found in the blood of most vertebrates [1][2][3][4]. The orthological proteins, synonymic name kininogen1, Uni Prot ID: P01042 for human, produced by splicing of the KNG1 gene transcript, is one of many proteins in the blood coagulation cascade pathways, in intrinsic pathway activation leading to thrombin generation partially independently from tissue factor (TF) extrinsic pathway, connecting blood coagulation with the kallikrein-kinin system (Figure 1).…”

What We Know About Kininogen Structure – Importance for Function and Perspectives from Cryo-EM

“…Kininogens or Fitzgerald factors are multidomain glycoproteins found in the blood of most vertebrates [1][2][3][4]. The orthological proteins, synonymic name kininogen-1, Uni-Prot ID: P01042 for human, produced by splicing of the KNG1 gene transcript, is one of many proteins in the blood coagulation cascade pathways, in intrinsic pathway activation leading to thrombin generation partially independently from tissue factor (TF) extrinsic pathway, connecting blood coagulation with the kallikrein-kinin system (Figure 1).…”