Serine protease zymogen

Protein G. This vitamin K-dependent glycoproteia serine protease zymogen is produced ia the Hver. It is an anticoagulant with species specificity (19—21). Proteia C is activated to Proteia by thrombomodulin, a proteia that resides on the surface of endothefial cells, plus thrombin ia the presence of calcium. In its active form, Proteia selectively iaactivates, by proteolytic degradation. Factors V, Va, VIII, and Villa. In this reaction the efficiency of Proteia is enhanced by complex formation with free Proteia S. la additioa, Proteia activates tissue plasminogen activator, which... 

Fig. 9.4 The coagulation cascade in the horseshoe crab amoebocyte lysate. In the presence of LPS, the Factor C serine protease zymogen is autocatalytically activated to an active form, Factor C , which activates the proenzyme Factor B into Factor B . This in turn activates proclotting to active clotting enzyme. Clotting enzyme then converts coagulogen into a coagulin gel clot, which traps the invading bacteria...

Factor C is the LPS-sensitive intracellular serine protease zymogen that initiates the coagulation cascade system. It exists as a single- and a double-chain form (Ding et al., 1993). While the catalytic site of the molecule is found in the light chain, the... 

S. Limulus Factor C endotoxin-sensitive serine protease zymogen with a mosaic structure of complement-like, epidermal growth factor-like and lectin-like domains. J Biol Chem 266... 

Protein C, another vitamin K-dependent serine protease zymogen in plasma, is a regulatory protein that, when activated, limits the activity of two activated procoagulant co-factors, factors Va and Villa. Heterozygotes for hereditary isolated protein C deficiency tend to develop a thrombotic disease which has been successfully treated with long-term coumarins (2,3). Apparently, the... 

Factor XI. Factor XI is a Hver-synthesized glycoprotein that circulates in a zymogen form as a dimer. It is converted to its active serine protease form by Factor Xlla in the presence of high molecular weight kininogen. Calcium is not required for this activation step. 

BLOOD CLOTTING. The formation of blood clots is the result of a series of zymogen activations (Figure 15.5). The amplification achieved by this cascade of enzymatic activations allows blood clotting to occur rapidly in response to injury. Seven of the clotting factors in their active form are serine proteases ... 

Plasmin, a serine protease (83 kDa), can degrade fibrin, and its degradation products (FDP) are soluble in the blood. Plasmin is formed from its proenzyme (zymogen, precursor), plasminogen (92 kDa), synthesized by the liver, and secreted into the blood circulation, where its concentration is 2 pM. Plasminogen is converted to plasmin by plasminogen activators (serine proteases). 

Factor XIa in the presence of activates factor IX (55 kDa, a zymogen containing vitamin K-dependent y-carboxyglutamate [Gla] residues see Chapter 45), to the serine protease, factor IXa. This in turn cleaves an Arg-Ile bond in factor X (56 kDa) to produce the two-chain serine protease, factor Xa. This latter reaction requires the assembly of components, called the tenase... 

Many coagulation factors are zymogens of serine proteases, becoming activated during the overall process. 

The digestive enzymes trypsin, chymotrypsin, elastase, and proteinase E are related serine proteases. All three are synthesized in the pancreas which secretes 5-10 g per day of proteins, mostly the inactive proenzymes (zymogens) of digestive enzymes.191,192... 

The serine proteases are a large family of proteolytic ( enzymes that use the reaction mechanism for nucleophilic catalysis outlined in equations (3) and (4), with a serine residue as the reactive nucleophile. The best known members of the family are three closely related digestive enzymes trypsin, chymotrypsin, and elastase. These enzymes are synthesized in the mammalian pancreas as inactive precursors termed zymogens. They are secreted into the small intestine, where they are activated by proteolytic cleavage in a manner discussed in chapter 9. 

Interactions between serine proteases are common, and substrates of serine proteases are usually other serine proteases that are activated from an inactive precursor [66]. The involvement of serine proteases in cascade pathways is well documented. One important example is the blood coagulation cascade. Blood clots are formed by a series of zymogen activations. In this enzymatic cascade, the activated form of one factor catalyzes the activation of the next factor. Very small amounts of the initial factors are sufficient to trigger the cascade because of the catalytic nature of the process. These numerous steps yield a large amplification, thus ensuring a rapid and amplified response to trauma. A similar mechanism is involved in the dissolution of blood clots. A third important example of the coordinated action of serine proteases is the intestinal digestive enzymes. The apoptosis pathway is another important example of coordinated action of other types of proteases. 

The destructive potential of proteases means that their activity has to be tightly regulated to prevent autolysis of protease-producing cells. Thus digestive proteases such as chymotrypsin, pepsin and trypsin are produced as inactive zymogens (proenzymes) and are subsequently activated after secretion. The serine protease-catalysed process of blood clotting involves a cascade of successive proteolytic activations of the blood clotting factor proteases involved [2-6]. 

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