Information AboutProtease |
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CLASSIFICATION There are six classes of proteases that are Currently known:
The threonine and glutamic acid proteases were not described until 1995 and 2004 , respectively. The mechanism used to cleave a peptide bond involves making an amino acid residue that has the cysteine and threonine (peptidases) or a water molecule (aspartic acid, metallo- and glutamic acid peptidases) nucleophilic so that it can attack the peptide Carbonyl group. One way to make a nucleophile is by a Catalytic Triad , where a Histidine residue is used to activate Serine , Cysteine or Threonine as a nucleophile. OCCURRENCE Proteases occur naturally in all organisms and constitute 1-5% of the gene content. These enzymes are involved in a multitude of physiological reactions from simple digestion of food proteins to highly regulated cascades (e.g., the Blood Clotting Cascade , the Complement System , Apoptosis pathways, and the invertebrate prophenoloxidase activating cascade). Peptidases can break either specific peptide bonds (''limited proteolysis''), depending on the Amino Acid sequence of a protein, or break down a complete peptide to amino acids (''unlimited proteolysis''). The activity can be a destructive change abolishing a protein's function or digesting it to its principal components; it can be an activation of a function or it can be a signal in a signalling pathway. Proteases are also a type of exotoxin, which is a virulence factor in bacteria pathogenesis. Bacteria exotoxic proteases destroy extracellular structures. Protease enzymes are also found used extensively in the bread industry in Bread Improver . PROTEASES (proteinases) are large group of ENZYMES - enzymes are the protein molecules which play the role of biocatalysts in the organism, they catalyse the reactions of all metabolic processes. Enzymes are divided into classes, one of which is the class of HYDROLASES - these enzymes catalyse the reaction of hydrolysis of various bonds (peptide bonds, ester bonds etc.) with the participation of a water molecule. PROTEOLYTIC ENZYMES (PROTEASES) belong to the class of HYDROLASES. Proteases are involved in splitting the peptide bonds which link the amino acid residues (elementar units of PROTEINS). Thus proteins are the SUBSTRATES for proteases. These enzymes "digest" long protein chain to shorter fragments. Some of them can detach the terminal amino acids from the protein chain (EXOPEPTIDASES - like aminopeptidases, carboxipeptidase A), the others "attack" internal peptide bonds of a protein (ENDOPEPTIDASES - like trypsin, chymotrypsin, pepsin, papain, elastase). Proteases are divided into four major groups according to the character of their active site (catalytic site) and conditions of action: serine proteinases, cysteine (thiol) proteinases, aspartic proteinases and METALLOPROTEINASES. Attachment of a protease to a certain group depends on the structure of catalytic site and the amino acid (as one of the constituents) essential for its activity. Proteases are everywhere and they are involved in various metabolic processes. Acid proteases secreted into the stomach (such as PEPSIN) and serine proteases present in duodeum (TRYPSIN, CHYMOTRYPSIN), enable us to digest the protein in food, proteases present in blood serum (THROMBIN, PLASMIN, HAGEMAN FACTOR etc.) play important role in blood clotting, as well as lysis of the clots, and the correct action of the immune system. Other proteases are present in leukocytes (ELASTASE, CATHEPSIN G) and play several different roles in metabolic control. Proteases determine the lifetime of other proteins playing important physiological role like hormones, antibodies, or other enzymes - this is one of the fastest "switching on" and "switching off" regulatory mechanisms in the physiology of an organism. By complex cooperative action the proteases may proceed as "cascade" reactions which result in amplification of the organism response to the physiological signal, and make this response very fast. INHIBITORS The function of peptidases is inhibited by Protease Inhibitor enzymes. Examples of protease inhibitors are the class of Serpin s (''ser''ine ''p''rotease or ''p''eptidase ''in''hibitors), incorporating Alpha 1-antitrypsin . Other serpins are Complement 1-inhibitor , Antithrombin , Alpha 1-antichymotrypsin , Plasminogen Activator Inhibitor 1 ( Coagulation , Fibrinolysis ) and the recently discovered Neuroserpin . Natural protease inhibitors include the family of Lipocalin proteins, which play a role in cell regulation and differentiation. Lipophilic ligands, attached to lipocalin proteins, have been found to possess tumor protease inhibiting properties. The natural Protease Inhibitor s are not to be confused with the Protease Inhibitor s used in antiretroviral therapy. Some Virus es, with HIV among them, depend on proteases in their reproductive cycle. Thus, Protease Inhibitor s are developed as Antiviral means. DEGRADATION Proteases, being themselves proteins, are known to be cleaved by other protease molecules, sometimes of the same variety. This may be an important method of regulation of peptidase activity. PROTEASE RESEARCH The field of protease research is enormous. Barrett and Rawlings estimated that approximately 8000 papers related to this field are published each year. For a look at current activities and interests of protease researchers, see the International Proteolysis Society web page. REFERENCES
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