Protease - AbsoluteAstronomy.com

A protease is any enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

that conducts proteolysis

Proteolysis

Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...

, that is, begins protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

catabolism

Catabolism

Catabolism is the set of metabolic pathways that break down molecules into smaller units and release energy. In catabolism, large molecules such as polysaccharides, lipids, nucleic acids and proteins are broken down into smaller units such as monosaccharides, fatty acids, nucleotides, and amino...

by hydrolysis

Hydrolysis

Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...

of the peptide bond

Peptide bond

This article is about the peptide link found within biological molecules, such as proteins. A similar article for synthetic molecules is being created...

s that link amino acid

Amino acid

Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s together in the polypeptide chain forming the protein.

Standard

Proteases are classified into six broad groups:

Serine protease
Serine protease
Serine proteases are enzymes that cleave peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the active site.They are found ubiquitously in both eukaryotes and prokaryotes...

s
Threonine protease
Threonine protease
Threnonine proteases are a family of proteolytic enzymes harbouring a threonine residue within the active site.The prototype members of this class of enzymes are the catalytic subunits of the proteasome....

s
Cysteine protease
Cysteine protease
Proteases are enzymes that degrade polypeptides. Cysteine proteases have a common catalytic mechanism that involves a nucleophilic cysteine thiol in a catalytic dyad. The first step is deprotonation of a thiol in the enzyme's active site by an adjacent amino acid with a basic side chain, usually a...

s
Aspartate protease
Aspartate protease
Aspartic proteases are a family of protease enzymes that use an aspartate residue for catalysis of their peptide substrates. In general, they have two highly-conserved aspartates in the active site and are optimally active at acidic pH...

s
Metalloproteases
Glutamic acid proteases

The threonine

Threonine

Threonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...

and glutamic-acid

Glutamic acid

Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...

proteases were not described until 1995 and 2004, respectively. The mechanism used to cleave a peptide bond

Peptide bond

This article is about the peptide link found within biological molecules, such as proteins. A similar article for synthetic molecules is being created...

involves making an amino acid residue that has the cysteine

Cysteine

Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...

and threonine (proteases) or a water molecule (aspartic acid

Aspartic acid

Aspartic acid is an α-amino acid with the chemical formula HOOCCHCH2COOH. The carboxylate anion, salt, or ester of aspartic acid is known as aspartate. The L-isomer of aspartate is one of the 20 proteinogenic amino acids, i.e., the building blocks of proteins...

, metallo- and glutamic acid proteases) nucleophilic so that it can attack the peptide carboxyl group. One way to make a nucleophile is by a catalytic triad

Catalytic triad

A catalytic triad refers to the three amino acid residues found inside the active site of certain protease enzymes: serine , aspartate , and histidine . They work together to break peptide bonds on polypeptides. In general terms, catalytic triad can refer to any set of three residues that function...

, where a histidine

Histidine

Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...

residue is used to activate serine

Serine

Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...

, cysteine

Cysteine

, or threonine

Threonine

Threonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...

as a nucleophile.

Within each of the broad groups proteases have been classified, by Rawlings and Barrett, into families of related proteases. For example within the serine

Serine

proteases families are labelled Sx where S denotes the serine catalytic type and the x denotes the number of the family, for example S1 (chymotrypsin

Chymotrypsin

Chymotrypsin is a digestive enzyme that can perform proteolysis. Chymotrypsin preferentially cleaves peptide amide bonds where the carboxyl side of the amide bond is a tyrosine, tryptophan, or phenylalanine. These amino acids contain an aromatic ring in their sidechain that fits into a...

s). An up to date classification of proteases into families is found in the MEROPS database.

By optimal pH

Alternatively, proteases may be classified by the optimal pH

In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...

in which they are active:

Acid proteases
Neutral proteases involved in type 1 hypersensitivity. Here, it is released by mast cell
Mast cell
A mast cell is a resident cell of several types of tissues and contains many granules rich in histamine and heparin...

s and causes activation of complement
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...

and kinins. This group includes the calpains.
Basic proteases (or alkaline proteases)

Occurrence

Proteases occur naturally in all organisms. 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

Coagulation

Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...

, the complement system

Complement system

The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...

, apoptosis

Apoptosis

Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

pathways, and the invertebrate prophenoloxidase-activating cascade). Proteases can either break specific peptide bonds (limited proteolysis), depending on the amino acid

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 signaling pathway.

Bacteria also secrete proteases to hydrolyse (digest) the peptide bonds in proteins and therefore break the proteins down into their constituent monomer

Monomer

A monomer is an atom or a small molecule that may bind chemically to other monomers to form a polymer; the term "monomeric protein" may also be used to describe one of the proteins making up a multiprotein complex...

s. Bacterial and fungal proteases are particularly important to the global carbon

Carbon

Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...

and nitrogen

Nitrogen

Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...

cycles in the recycling of proteins, and such activity tends to be regulated in by nutritional signals in these organisms. The net impact of nutritional regulation of protease activity among the thousands of species present in soil can be observed at the overall microbial community level as proteins are broken down in response to carbon, nitrogen, or sulfur limitation.

A secreted bacterial protease may also act as an exotoxin, and be an example of a virulence factor

Virulence factor

Virulence factors are molecules expressed and secreted by pathogens that enable them to achieve the following:* colonization of a niche in the host...

in bacterial pathogenesis

Pathogenesis

The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...

. Bacterial exotoxic proteases destroy extracellular structures. Protease enzymes are also used extensively in the bread industry in bread improver

Bread improver

Bread improver has been a common ingredient in bread since the early 1950s, and is used to speed up bread production.- History :Before the 1950s, bread had been made virtually the same way since it was first discovered. Using sourdoughs, and sponge and dough methods, bread would take up to a day to...

.

Proteases, also known as proteinases or proteolytic enzymes, are a large group of enzymes. Proteases belong to the class of enzymes known as hydrolases, which catalyse the reaction of hydrolysis

Hydrolysis

of various bonds with the participation of a water molecule.

Proteases are involved in digesting long protein chains into short fragments, splitting the peptide bonds that link amino acid

Amino acid

residues. Some of them can detach the terminal amino acids from the protein chain (exopeptidases, such as aminopeptidase

Aminopeptidase

Aminopeptidase is a zinc-dependent enzyme produced and secreted by glands of the small intestine. It helps the enzymatic digestion of proteins. Additional digestive enzymes produced by these glands include dipeptidases, maltase, sucrase, lactase, and enterokinase.Aminopeptidases catalyze the...

s, carboxypeptidase A

Carboxypeptidase A

Carboxypeptidase A usually refers to the pancreatic exopeptidase which hydrolyzes peptide bonds of C-terminal residues with aromatic or aliphatic side chains...

); the others attack internal peptide bonds of a protein (endopeptidases, such as trypsin

Trypsin

Trypsin is a serine protease found in the digestive system of many vertebrates, where it hydrolyses proteins. Trypsin is produced in the pancreas as the inactive proenzyme trypsinogen. Trypsin cleaves peptide chains mainly at the carboxyl side of the amino acids lysine or arginine, except when...

, chymotrypsin

Chymotrypsin

, pepsin

Pepsin

Pepsin is an enzyme whose precursor form is released by the chief cells in the stomach and that degrades food proteins into peptides. It was discovered in 1836 by Theodor Schwann who also coined its name from the Greek word pepsis, meaning digestion...

, papain

Papain

Papain, also known as papaya proteinase I, is a cysteine protease enzyme present in papaya and mountain papaya .-Papain family:...

, elastase

Elastase

In molecular biology, elastase is an enzyme from the class of proteases that break down proteins.- Forms and classification:There exist eight human genes for elastase:Bacterial forms: Organisms such as P...

).

Proteases are divided into four major groups according to the character of their catalytic active site

Active site

In biology the active site is part of an enzyme where substrates bind and undergo a chemical reaction. The majority of enzymes are proteins but RNA enzymes called ribozymes also exist. The active site of an enzyme is usually found in a cleft or pocket that is lined by amino acid residues that...

and conditions of action: serine proteinases, cysteine (thiol) proteinases, aspartic proteinases, and metalloproteinase

Metalloproteinase

Metalloproteinases constitute a family of enzymes from the group of proteases, classified by the nature of the most prominent functional group in their active site. These are proteolytic enzymes whose catalytic mechanism involves a metal. Most metalloproteases are zinc-dependent, but some use...

s. 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 used throughout an organism for various metabolic processes. Acid proteases secreted into the stomach (such as pepsin

Pepsin

) and serine proteases present in duodenum

Duodenum

The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...

(trypsin

Trypsin

and chymotrypsin

Chymotrypsin

) enable us to digest the protein in food; proteases present in blood serum (thrombin

Thrombin

Thrombin is a "trypsin-like" serine protease protein that in humans is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the first step of the coagulation cascade, which ultimately results in the stemming of blood loss...

, plasmin

Plasmin

Plasmin is an important enzyme present in blood that degrades many blood plasma proteins, most notably, fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein is encoded by the PLG gene.- Function :...

, 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

Elastase

, cathepsin G

Cathepsin G

Cathepsin G is an enzymatic protein belonging to the peptidase or protease families. In humans, it is coded by the CTSG gene.The protein encoded by this gene, a member of the peptidase S1 protein family, is found in azurophil granules of neutrophilic polymorphonuclear leukocytes...

) 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 rapid and efficient amplification of an organism's response to a physiological signal.

Proteases are part of many laundry detergent

Laundry detergent

Laundry detergent, or washing powder, is a substance that is a type of detergent that is added for cleaning laundry. In common usage, "detergent" refers to mixtures of chemical compounds including alkylbenzenesulfonates, which are similar to soap but are less affected by "hard water." In most...

Inhibitors

The activity of proteases is inhibited by protease inhibitor

Protease inhibitor (biology)

In biology and biochemistry, protease inhibitors are molecules that inhibit the function of proteases. Many naturally occurring protease inhibitors are proteins....

s. One example of protease inhibitors is the serpin

Serpin

Serpins are a group of proteins with similar structures that were first identified as a set of proteins able to inhibit proteases. The acronym serpin was originally coined because many serpins inhibit chymotrypsin-like serine proteases .The first members of the serpin superfamily to be extensively...

superfamily, which includes alpha 1-antitrypsin

Alpha 1-antitrypsin

Alpha 1-Antitrypsin or α1-antitrypsin is a protease inhibitor belonging to the serpin superfamily. It is generally known as serum trypsin inhibitor. Alpha 1-antitrypsin is also referred to as alpha-1 proteinase inhibitor because it inhibits a wide variety of proteases...

, C1-inhibitor

C1-inhibitor

C1-inhibitor is a protease inhibitor belonging to the serpin superfamily. Its main function is the inhibition of the complement system to prevent spontaneous activation. C1-inhibitor is an acute-phase protein that circulates in blood at levels of around 0.25 g/L. The levels rise ~2-fold during...

, antithrombin

Antithrombin

Antithrombin is a small protein molecule that inactivates several enzymes of the coagulation system. Antithrombin is a glycoprotein produced by the liver and consists of 432 amino acids. It contains three disulfide bonds and a total of four possible glycosylation sites...

, alpha 1-antichymotrypsin

Alpha 1-antichymotrypsin

Alpha 1-antichymotrypsin is an alpha globulin glycoprotein that is a member of the serpin superfamily.It inhibits the activity of certain enzymes called proteases, such as cathepsin G that is found in neutrophils, and chymases found in mast cells, by cleaving them into a different shape or...

, plasminogen activator inhibitor-1, and neuroserpin.

Natural protease inhibitors include the family of lipocalin

Lipocalin

The lipocalins are a family of proteins which transport small hydrophobic molecules such as steroids, bilins, retinoids, and lipids. They share limited regions of sequence homology and a common tertiary structure architecture...

proteins, which play a role in cell regulation and differentiation. Lipophilic

Lipophilic

Lipophilicity, , refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. These non-polar solvents are themselves lipophilic — the axiom that like dissolves like generally holds true...

ligands, attached to lipocalin proteins, have been found to possess tumor protease inhibiting properties. The natural protease inhibitor

Protease inhibitor (biology)

In biology and biochemistry, protease inhibitors are molecules that inhibit the function of proteases. Many naturally occurring protease inhibitors are proteins....

s are not to be confused with the protease inhibitor

Protease inhibitor (pharmacology)

Protease inhibitors are a class of drugs used to treat or prevent infection by viruses, including HIV and Hepatitis C. PIs prevent viral replication by inhibiting the activity of proteases, e.g.HIV-1 protease, enzymes used by the viruses to cleave nascent proteins for final assembly of new...

s used in antiretroviral therapy. Some viruses, with HIV

HIV

Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...

among them, depend on proteases in their reproductive cycle. Thus, protease inhibitor

Protease inhibitor (pharmacology)

s are developed as antiviral

Antiviral drug

Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...

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 protease 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.

External links

The source of this article is wikipedia, the free encyclopedia. The text of this article is licensed under the GFDL.

Standard

By optimal pH

Occurrence

Inhibitors

Degradation

Protease research

See also

External links