PROTEASE

CAS NUMBER: 9001-92-7

Protease (also called a peptidase or proteinase) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, the breakdown of proteins into smaller polypeptides or single amino acids. 
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 (breakdown of old proteins), and cell signaling.
In the absence of functional accelerants, proteolysis would be very slow, taking hundreds of years. 
Proteases can be found in all forms of life and viruses. 
They have independently evolved multiple times, and different classes of protease can perform the same reaction by completely different catalytic mechanisms.
Proteases were first grouped into 84 families according to their evolutionary relationship in 1993, and classified under four catalytic types: serine, cysteine, aspartic, and metallo proteases. 
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 (proteases) or a water molecule (aspartic acid, metallo- and acid proteases) nucleophilic so that it can attack the peptide carboxyl 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. 
This is not an evolutionary grouping, however, as the nucleophile types have evolved convergently in different superfamilies, and some superfamilies show divergent evolution to multiple different nucleophiles.

Proteases occur in all organisms, from prokaryotes to eukaryotes to virus. 
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). 
Proteases can either break specific peptide bonds (limited proteolysis), depending on the amino acid sequence of a protein, or completely break down a peptide to amino acids (unlimited proteolysis). 
The activity can be a destructive change (abolishing a protein's function or digesting Protease to its principal components), Protease can be an activation of a function, or Protease can be a signal in a signaling pathway.
The activity of proteases is inhibited by protease inhibitors. 
One example of protease inhibitors is the serpin superfamily. 

Protease includes alpha 1-antitrypsin (which protects the body from excessive effects of its own inflammatory proteases), alpha 1-antichymotrypsin (which does likewise), C1-inhibitor (which protects the body from excessive protease-triggered activation of its own complement system), antithrombin (which protects the body from excessive coagulation), plasminogen activator inhibitor-1 (which protects the body from inadequate coagulation by blocking protease-triggered fibrinolysis), and 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 inhibitors are not to be confused with the protease inhibitors used in antiretroviral therapy. 
Some viruses, with HIV/AIDS among them, depend on proteases in their reproductive cycle. 
Thus, protease inhibitors are developed as antiviral means.
Other natural protease inhibitors are used as defense mechanisms. 
Common examples are the trypsin inhibitors found in the seeds of some plants, most notable for humans being soybeans, a major food crop, where they act to discourage predators. 
Raw soybeans are toxic to many animals, including humans, until the protease inhibitors they contain have been denatured.

Protease is the name given to a class of enzymes that catalyze protein catabolism by hydrolysis of the peptide bonds linking amino acids together. 
Proteases have evolved to perform these reactions by numerous different mechanisms and are found in animals, plants, bacteria, archaea, and viruses, highlighting the important role that they play in all forms of life on Earth. 
Proteases are involved in protein processing, regulation of protein function, apoptosis, viral pathogenesis, digestion, photosynthesis, and numerous other vital processes.

Proteases also offer a valuable target in many therapeutic settings, including Alzheimer’s, cancer, and viral infection. 
In fact, one of the most widely-used classes of anti-viral therapeutics is protease inhibitors, which are used to treat both HIV and HCV infections.
Protease is an enzyme that catalyzes the hydrolysis of proteins. 
Protease does this by breaking down peptide bonds between amino acids. 
This enzyme is used in bakery products as a dough conditioner. 
Protease modifies dough rheology and handling properties, improving:

-Workability
-Pliability
-Machinability
-The quality of the finished products

Proteolytic enzymes (proteases) are enzymes that break down protein. 
These enzymes are made by animals, plants, fungi, and bacteria.
Protease refers to a group of enzymes whose catalytic function is to hydrolyze peptide bonds of proteins. 
They are also called proteolytic enzymes or proteinases. 
Proteases differ in their ability to hydrolyze various peptide bonds. 
Proteases also have many functions. 
The action of proteases was believed to be restricted to digestive purposes, extracellular modeling and/or remodeling of tissues, mainly through proteolytic activity on interstitial molecules, occurring throughout homeostasis and development or, in aberrant maladaptive circumstances, during disease pathogenesis.

Proteases are involved in many aspects of human biology. For example, in the small intestine, proteases digest dietary proteins to allow absorption of amino acids. 
Other processes mediated by proteases include blood coagulation, immune function, maturation of prohormones, bone formation, programmed cell death and the recycling of cellular proteins that are no longer needed.
Proteases are not merely restricted to digestive purposes and remodeling of extracellular matrix and tissues, but are also key factors for the induction of physiological immune responses. 
This induction can be direct, through the degradation of pathogens within phagolysosomes, or indirect, through the activation of key pattern recognition receptors (PRRs), such as toll-like receptors (TLRs). 
Unfortunately, excess production of proteases leads to maladaptive host responses and excess tissue inflammation and damage.
Proteases also offer a valuable target in many therapeutic settings, including Alzheimer's, cancer, and viral infection. 
MMP-9, a matrix metallopeptidase, plays a role in angiogenesis and is a therapeutic target for cancer. 
Because of their significance in the pathology of disease, proteases are a relevant drug target class.
Some proteolytic enzymes that may be found in supplements include bromelain, chymotrypsin, ficin, papain, serrapeptase, and trypsin.

Proteolytic enzymes are used for a long list of conditions including cleaning wounds on the skin, help with digestion, pain and swelling, and many other conditions.
Proteases are classified by the amino acids or ligands that catalyze the hydrolysis reaction. 
For example, serine proteases contain a serine in the active site. The serine is helped by a neighboring histidine and aspartic acid. 
This combination is called the catalytic triad, and is conserved in all serine proteases. 
Serine proteases work in a two step fashion; first, they form a covalent bond with the protein to be cleaved; in the second step, water comes in and releases the second half of the cleaved protein. 
Cysteine proteases use cysteine as a nucleophile just like serine proteases use serine as a nucleophile.
Protease is a natural biological catalyst. 
Protease can be extracted from cereals and fruits, such as papain or bromelain. 
Or, Protease comes from animal sources like chymosin or rennin from bovines.

Proteases, also called peptidase or proteinase, are a kind of simple destructive enzymes necessary for protein catabolism and the generation of amino acids in primitive organisms by hydrolyzing peptide bonds. 
Proteases are likely to arise at the earliest stages of protein evolution and have been applied for multiple times. 
Different classes of protease usually perform the same proteolysis reaction through completely different catalytic mechanisms. 
Proteases can be found in a wild of sources like animalia, plantae, fungi, bacteria, archaea and viruses and they participate in many body processes including digestion, immune system function, and blood circulation.
Protease enzymes improve the digestibility and availability of proteins, optimising diet costs by allowing lower quality protein alternatives to be used in the diet. 
This helps save on feed costs, as grain and oilseed meal prices continue to fluctuate. Researchers have also been digging into the additional benefits of the protease enzyme and its link to gut health and bacteria balance in poultry and swine.
Protease enzymes are an important factor in protein digestion as they hydrolyse the less digestible proteins in animal feeds and break them down into more usable peptides. 
Improving dietary protein digestibility with a quality protease can reduce feed cost by allowing the use of lower crude protein feedstuffs with lesser quality amino acids, effectively lowering protein and digestible amino acids levels required from the feedstuffs up to 10%.

FUNCTION:

Protease has been a long time that studies on proteases have mainly focused on their original roles as blunt aggressors for protein demolition. 
Beyond these nonspecific degradative functions, proteases also catalyze highly specific reactions of proteolytic processing to produce new protein products, which inaugurates a new era in protease research. 
A large collection of findings have demonstrated the relevance of proteases in the control of multiple biological processes in all living organisms through regulating the fate, localization, and activity of many proteins, modulating protein-protein interactions, creating new bioactive molecules, contributing to the processing of cellular information, and generating, transducing, and amplifying molecular signals. 
As a result of these multiple actions, proteases could thereby influence replication and transcription of DNA, proliferation and differentiation of cell, morphogenesis and remodeling of tissue, heat shock and unfolded protein responses, inflammation, immunity, apoptosis, and so on.

USES:

The field of protease research is enormous. 
Since 2004, approximately 8000 papers related to this field were published each year. 
Proteases are used in industry, medicine and as a basic biological research tool.
Digestive proteases are part of many laundry detergents and are also used extensively in the bread industry in bread improver. 
A variety of proteases are used medically both for their native function (e.g. controlling blood clotting) or for completely artificial functions (e.g. for the targeted degradation of pathogenic proteins). 
Highly specific proteases such as TEV protease and thrombin are commonly used to cleave fusion proteins and affinity tags in a controlled fashion.

INDUSTRIAL USES:

Proteases have commercial importance in different industrial and applied sectors and have multiple applications. 
Due to their wide variety of physiological characteristics, including hydrolysis at pH extremes or elevated temperatures, they ideal for use in the pharmaceutical, diagnostic, textile, food and beverage sectors. 
Specific applications for these proteases include but are not limited to; dietary fiber testing and clean-in-place additives for contaminate removal. 
We have a wide range of purified enzymes and enzyme mixtures for researching and developing new processes, products, and assays.

FUNCTION:

Proteases are involved in digesting long protein chains into shorter fragments by splitting the peptide bonds that link amino acid residues. 
Some detach the terminal amino acids from the protein chain (exopeptidases, such as aminopeptidases, carboxypeptidase A); others attack internal peptide bonds of a protein (endopeptidases, such as trypsin, chymotrypsin, pepsin, papain, elastase).

SPECIFICITY:

Proteolysis can be highly promiscuous such that a wide range of protein substrates are hydrolysed. 
This is the case for digestive enzymes such as trypsin which have to be able to cleave the array of proteins ingested into smaller peptide fragments. 
Promiscuous proteases typically bind to a single amino acid on the substrate and so only have specificity for that residue. 
Conversely some proteases are highly specific and only cleave substrates with a certain sequence. 
Blood clotting (such as thrombin) and viral polyprotein processing (such as TEV protease) requires this level of specificity in order to achieve precise cleavage events. 
This is achieved by proteases having a long binding cleft or tunnel with several pockets along it which bind the specified residues.

APPLICATION:

Protease is called a micro ingredient in baking. 
Protease is favored in breadmaking systems that don’t require fermentation steps such as yeast preferments or sourdough. 
The addition of specialty enzymes is how high-quality artisan and variety bread can be made in a short time.
Usually, protease is added during dough mixing. 
Depending on the application and formulation, levels are 0.1 to 0.5% based on flour weight. 

Protease is also used in clean label applications. There can be issues with purity, such as side reactions and secondary activity. 
Also, ensuring complete inactivation during baking is very important for optimal performance. 
When supplying protease, Protease is a good practice to conduct baking tests and lab analysis prior to line production.
Similar to other enzymes, protease requires special conditions for optimum activity and performance.
The research value of protease is enormous and proteases have been widely applied in industry, medicine and biological technology. 
In compliance with the essential roles of proteases in living organisms, minor alterations in proteolytic systems would underlie multiple pathological conditions such as neurodegenerative disorder, cancer, cardiovascular and inflammatory diseases. 
Therefore, proteases accordingly play significant roles in pharmaceutical industry as potential drug targets or as diagnostic and prognostic biomarkers. 
A variety of proteases are applied medically both for their native function or completely artificial functions. 

Proteases also contribute to the processing, maturation, or destruction of specific sets of plant proteins as a reflection of developmental cues or environmental variations. 
Similarly, many infectious microorganisms take proteases as necessities for replication or treat them as virulence factors, which expedited the development of protease-targeted therapies for the administration of diseases with great relevance to human life. 
Proteases are also the major focus in the biotechnological industry owing to their usefulness as biochemical reagents or in the manufacture of numerous products. 
Digestive proteases as part of many laundry detergents can also be used extensively in the bread industry as bread improver.

Applications

- Isolation of genomic DNA from mouse tail
- Isolation of genomic DNA from cultured cells
- Removal of DNases and RNases when isolating DNA and RNA from tissues or cell lines
- Determination of enzyme localization
- Improving cloning efficiency of PCR products

PHYSICAL AND CHEMICAL PROPERTIES:

-storage temperature: 2-8°C
-solubility H2O: 5-20 mg/mL
-form: powder
-color: white

PRODUCTION:

On the other hand, Protease can be more efficiently produced from food-grade microorganisms. 
Some examples are fungi (Aspergillus oryzae) or bacteria (Bacillus subtilis). 
This happens through industrial-scale fermentation and downstream processing.

HOW DOES IT WORK:

Proteolytic enzymes are enzymes that break down proteins in the body or on the skin. 
This might help with digestion or with the breakdown of proteins involved in swelling and pain.

SYNONYM:

Cysteine Protease inhibitor (hydrochloride)
Cysteine protease inhibitor HCl
HY-17541A
MFCD28167760
Cysteine Protease inhibitor hydrochloride
2197053-49-7

IUPAC NAME:

proteases with the exception of those specified elsewhere in this Annex
Proteinase, Tritirachium album serine
proteinases
Proteolytc Enzyme