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Chymotrypsin (EC 3.4.21.1,chymotrypsins A and B,alpha-chymar ophth,avazyme,chymar,chymotest,enzeon,quimar,quimotrase,alpha-chymar,alpha-chymotrypsin A,alpha-chymotrypsin) is a digestive enzyme component of pancreatic juice acting in the duodenum,where it performs proteolysis,the breakdown of proteins and polypeptides. Chymotrypsin preferentially cleaves peptide amide bonds where the side chain of the amino acid N-terminal to the scissile amide bond (the P1 position) is a large hydrophobic amino acid (tyrosine,tryptophan,and phenylalanine). These amino acids contain an aromatic ring in their side chain that fits into a hydrophobic pocket (the S1 position) of the enzyme. It is activated in the presence of trypsin. The hydrophobic and shape complementarity between the peptide substrate P1 side chain and the enzyme S1 binding cavity accounts for the substrate specificity of this enzyme. Chymotrypsin also hydrolyzes other amide bonds in peptides at slower rates,particularly those containing leucine and methionine at the P1 position.
Trypsin is an enzyme in the first section of the small intestine that starts the digestion of protein molecules by cutting these long chains of amino acids into smaller pieces. It is a serine protease from the PA clan superfamily,found in the digestive system of many vertebrates,where it hydrolyzes proteins. Trypsin is formed in the small intestine when its proenzyme form,the trypsinogen produced by the pancreas,is activated. Trypsin cuts peptide chains mainly at the carboxyl side of the amino acids lysine or arginine. It is used for numerous biotechnological processes. The process is commonly referred to as trypsin proteolysis or trypsinization,and proteins that have been digested/treated with trypsin are said to have been trypsinized. Trypsin was discovered in 1876 by Wilhelm Kühne and was named from the Ancient Greek word for rubbing since it was first isolated by rubbing the pancreas with glycerin.
A protease is an enzyme that catalyzes proteolysis,breaking down proteins into smaller polypeptides or single amino acids,and spurring the formation of new protein products. They do this by cleaving the peptide bonds within proteins by hydrolysis,a reaction where water breaks bonds. Proteases are involved in many biological functions,including digestion of ingested proteins,protein catabolism,and cell signaling.
In biology and biochemistry,the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate and residues that catalyse a reaction of that substrate. Although the active site occupies only ~10–20% of the volume of an enzyme,it is the most important part as it directly catalyzes the chemical reaction. It usually consists of three to four amino acids,while other amino acids within the protein are required to maintain the tertiary structure of the enzymes.
In biology and biochemistry,protease inhibitors,or antiproteases,are molecules that inhibit the function of proteases. Many naturally occurring protease inhibitors are proteins.
Serine proteases are enzymes that cleave peptide bonds in proteins. Serine serves as the nucleophilic amino acid at the (enzyme's) active site. They are found ubiquitously in both eukaryotes and prokaryotes. Serine proteases fall into two broad categories based on their structure:chymotrypsin-like (trypsin-like) or subtilisin-like.
Urokinase,also known as urokinase-type plasminogen activator (uPA),is a serine protease present in humans and other animals. The human urokinase protein was discovered,but not named,by McFarlane and Pilling in 1947. Urokinase was originally isolated from human urine,and it is also present in the blood and in the extracellular matrix of many tissues. The primary physiological substrate of this enzyme is plasminogen,which is an inactive form (zymogen) of the serine protease plasmin. Activation of plasmin triggers a proteolytic cascade that,depending on the physiological environment,participates in thrombolysis or extracellular matrix degradation. This cascade had been involved in vascular diseases and cancer progression.
Enteropeptidase is an enzyme produced by cells of the duodenum and is involved in digestion in humans and other animals. Enteropeptidase converts trypsinogen into its active form trypsin,resulting in the subsequent activation of pancreatic digestive enzymes. Absence of enteropeptidase results in intestinal digestion impairment.
A catalytic triad is a set of three coordinated amino acids that can be found in the active site of some enzymes. Catalytic triads are most commonly found in hydrolase and transferase enzymes. An acid-base-nucleophile triad is a common motif for generating a nucleophilic residue for covalent catalysis. The residues form a charge-relay network to polarise and activate the nucleophile,which attacks the substrate,forming a covalent intermediate which is then hydrolysed to release the product and regenerate free enzyme. The nucleophile is most commonly a serine or cysteine amino acid,but occasionally threonine or even selenocysteine. The 3D structure of the enzyme brings together the triad residues in a precise orientation,even though they may be far apart in the sequence.
Diisopropyl fluorophosphate (DFP) or Isoflurophate is an oily,colorless liquid with the chemical formula C6H14FO3P. It is used in medicine and as an organophosphorus insecticide. It is stable,but undergoes hydrolysis when subjected to moisture.
Dipeptidyl peptidase-4 (DPP4),also known as adenosine deaminase complexing protein 2 or CD26 is a protein that,in humans,is encoded by the DPP4 gene. DPP4 is related to FAP,DPP8,and DPP9. The enzyme was discovered in 1966 by Hopsu-Havu and Glenner,and as a result of various studies on chemism,was called dipeptidyl peptidase IV [DP IV].
In biochemistry,phenylmethylsulfonyl fluoride (PMSF) is a serine protease inhibitor commonly used in the preparation of cell lysates. PMSF does not inactivate all serine proteases. The effective concentration of PMSF is between 0.1 - 1 mM. The half-life is short in aqueous solutions. Stock solutions are usually made up in anhydrous ethanol,isopropanol,or corn oil and diluted immediately before use.
Subtilisin is a protease initially obtained from Bacillus subtilis.
Protein metabolism denotes the various biochemical processes responsible for the synthesis of proteins and amino acids (anabolism),and the breakdown of proteins by catabolism.
In molecular biology Proteinase K is a broad-spectrum serine protease. The enzyme was discovered in 1974 in extracts of the fungus Engyodontium album. Proteinase K is able to digest hair (keratin),hence,the name "Proteinase K". The predominant site of cleavage is the peptide bond adjacent to the carboxyl group of aliphatic and aromatic amino acids with blocked alpha amino groups. It is commonly used for its broad specificity. This enzyme belongs to Peptidase family S8 (subtilisin). The molecular weight of Proteinase K is 28,900 daltons.
Fibroblast activation protein alpha (FAP-alpha) also known as prolyl endopeptidase FAP is an enzyme that in humans is encoded by the FAP gene.
Dipeptidyl peptidase-4 inhibitors are enzyme inhibitors that inhibit the enzyme dipeptidyl peptidase-4 (DPP-4). They are used in the treatment of type 2 diabetes mellitus. Inhibition of the DPP-4 enzyme prolongs and enhances the activity of incretins that play an important role in insulin secretion and blood glucose control regulation. Type 2 diabetes mellitus is a chronic metabolic disease that results from inability of the β-cells in the pancreas to secrete sufficient amounts of insulin to meet the body's needs. Insulin resistance and increased hepatic glucose production can also play a role by increasing the body's demand for insulin. Current treatments,other than insulin supplementation,are sometimes not sufficient to achieve control and may cause undesirable side effects,such as weight gain and hypoglycemia. In recent years,new drugs have been developed,based on continuing research into the mechanism of insulin production and regulation of the metabolism of sugar in the body. The enzyme DPP-4 has been found to play a significant role.
Many major physiological processes depend on regulation of proteolytic enzyme activity and there can be dramatic consequences when equilibrium between an enzyme and its substrates is disturbed. In this prospective,the discovery of small-molecule ligands,like protease inhibitors,that can modulate catalytic activities has an enormous therapeutic effect. Hence,inhibition of the HIV protease is one of the most important approaches for the therapeutic intervention in HIV infection and their development is regarded as major success of structure-based drug design. They are highly effective against HIV and have,since the 1990s,been a key component of anti-retroviral therapies for HIV/AIDS.
Mannan-binding lectin-associated serine protease-2 is an enzyme. This enzyme catalyses the following chemical reaction
Nancy A. Thornberry is the founding CEO and current Chair,R&D at Kallyope Inc. in New York City. She previously worked with Merck Research Laboratories (MRL),joining the company in 1979 as a biochemist and retiring from the position of Senior Vice President and Franchise Head,Diabetes and Endocrinology in 2013.
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- ↑ "National Academy of Inventors".