Protease

Peptidases ( short form of peptide bond hydrolases ) are enzymes that can cleave proteins or peptides. They catalyze the hydrolysis of peptide bonds. Peptidases are often, especially when larger proteins are cleaved, termed proteases, proteinases or proteolytic enzymes.

• 2.1 EC nomenclature
• 2.2 Nature of the catalyzed proteolytic reaction
• 2.3 Types of the active site ( MEROPS )

Occurrence and function

Peptidases are ubiquitous, that is, they come in all tissues and cells of all organisms. We distinguish intracellular and extracellular peptidases.

Intracellular peptidases take in numerous cellular compartments different tasks. So they participate in the regulation of the protein content of the cell:

• Proteins are transferred to the preparation (see protein ) by cleavage of the peptide fragments in the active state.
• Signal peptidases cleave signal peptides from proteins and thus ensure that intracellularly synthesized proteins are directed to their right of use on.
• Peptidases are involved in the processing of antigens. An important role is played here a large, existing multi-subunit Peptidasekomplex, called the proteasome.
• If proteins are no longer needed or are damaged, they are degraded by peptidases in the lysosomes. All eukaryotic cells also have an ATP-dependent proteolytic system, which is localized in the cytosol.

Extracellular, secreted peptidases are found in animal organisms, especially in the digestive tract, where they catalyze the hydrolytic cleavage of foods. However, they are also found in other extracellular fluids, where they take part, highly specific tasks, such as the peptidases of the coagulation system, the complement system and the fibrinolytic system.

Peptidases themselves can (removal of part of the molecule ) are activated by limited proteolysis. By peptidase inhibitors, low molecular weight substances, such as pepstatin, iodoacetate or phenanthroline to inhibit peptidases leave in their function.

Importance of peptidases in tumor formation

Peptidases play an important role in metastasis of malignant tumors. For the development of metastases of malignant solid tumors, it is necessary that tumor cells, the basement membrane consisting of collagen (type IV), laminin and heparin sulfate proteoglycans wander through. For overcome these peptidases play like serine proteinases, cathepsin proteinases and matrix metalloproteinases play an essential role.

Classification of peptidases

EC nomenclature

Peptidases, like all other enzymes also divided into groups by means of the so-called EC classification. Peptidases belong to the class 3 of hydrolases and form the subclass 3.4. This is in turn divided into 14 sub - subclasses. Basis of this nomenclature is the type of reaction catalyzed and the active site.

Type of reaction catalyzed proteolytic

Since enzymes are able to catalyze a wide variety of chemical reactions, it is logical sense to classify them on the basis of these reactions. A first classification of peptidases under enzymological point of view is the. Exopeptidases and endopeptidases in

Exopeptidases cleave the polypeptide from the ends. Those which operate at the N -terminus, are referred to depending on the cleaved fragment as aminopeptidases ( removal of a single amino acid ), dipeptidyl peptidase ( release of a dipeptide ) or tripeptidyl - peptidases ( release one tripeptide ). At the C -terminus acting individual amino exopeptidases ( carboxypeptidases ) or dipeptides set free ( peptidyl- dipeptidases ). Moreover, there are exopeptidases which cleave dipeptides ( dipeptidases ) or terminal substituted, cyclized or linked via isopeptide bonds can remove amino acids (omega- peptidases ).

Endopeptidases cleave mostly at very specific sites within the polypeptide chain. Classification on the basis of satisfactory specificity is not possible. Here, therefore, the division on the basis of the active site ( see below). The length of the polypeptide to be split may vary in a wide range endopeptidases. Most proteins are the substrates. However, there are a group of endopeptidases that are dedicated to shorter peptides as substrate ( oligopeptidases ).

Nature of the active site ( MEROPS )

The subdivision of peptidases according to the EC system has shortcomings. Thus, the number of endopeptidases are represented by only six sub - subclasses. Various peptidases can be found here in the same group again. The most serious disadvantage is that structural, evolutionary similarities between the individual enzymes are not observed.

For this purpose, 1993 by Neil D. Rawlings and Alan J. Barrett a new classification scheme, called MEROPS introduced that takes into account structural aspects and evolutionary relationships based on the amino acid sequence.

Peptidases have, like all enzymes, active center, the respective reaction - in this case, the hydrolysis of peptide bonds - possible. Within these centers are some, or groups of amino acids essential for the functionality. Therefore peptidases in MEROPS database are based on the chemical nature of their catalytic active sites classified into six groups ( see table below):

Peptidases in the overview

Acrosin, Aminopeptidase B, bromelain, calpain I, carboxypeptidase A, cathepsin A, Cathepsin B, Cathepsin D, Cathepsin E, Cathepsin K, Chymotrypsin, Collagenase, dipeptidyl peptidase- 4, dispase, elastase, factor IIa, factor Xa, ficin, gpr endopeptidase, HIV protease, kallikrein, MBTPS1, papain, pepsin, plasmin, Prepilin type IV peptidase, prolyl oligopeptidase, proteinase K, proteasome, renin, secretases (alpha -, beta - and gamma -secretase ), thermolysin, thrombin, trypsin, urokinase