Collagenases are

enzymes An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as pro ...

that break the

peptide bonds In organic chemistry, a peptide bond is an amide type of covalent chemical bond linking two consecutive alpha-amino acids from C1 (carbon number one) of one alpha-amino acid and N2 (nitrogen number two) of another, along a peptide or protein chai ...

collagen Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...

. They assist in destroying extracellular structures in the pathogenesis of bacteria such as ''

Clostridium ''Clostridium'' is a genus of anaerobic, Gram-positive bacteria. Species of ''Clostridium'' inhabit soils and the intestinal tracts of animals, including humans. This genus includes several significant human pathogens, including the causative ...

''. They are considered a

virulence factor Virulence factors (preferably known as pathogenicity factors or effectors in botany) are cellular structures, molecules and regulatory systems that enable microbial pathogens (bacteria, viruses, fungi, and protozoa) to achieve the following: * c ...

, facilitating the spread of

gas gangrene Gas gangrene (also known as clostridial myonecrosis) is a bacterial infection that produces tissue gas in gangrene. This deadly form of gangrene usually is caused by '' Clostridium perfringens'' bacteria. About 1,000 cases of gas gangrene are r ...

. They normally target the connective tissue in

muscle cells A muscle cell, also known as a myocyte, is a mature contractile cell in the muscle of an animal. In humans and other vertebrates there are three types: skeletal, smooth, and cardiac (cardiomyocytes). A skeletal muscle cell is long and threadli ...

and other body organs. Collagen, a key component of the animal extracellular matrix, is made through

cleavage Cleavage may refer to: Science * Cleavage (crystal), the way in which a crystal or mineral tends to split * Cleavage (embryo), the division of cells in an early embryo * Cleavage (geology), foliation of rock perpendicular to stress, a result of ...

of pro-collagen by collagenase once it has been secreted from the cell. This stops large structures from forming inside the cell itself. In addition to being produced by some bacteria, collagenase can be made by the body as part of its normal immune response. This production is induced by

cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

s, which stimulate cells such as

fibroblasts A fibroblast is a type of biological cell typically with a spindle shape that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibrobla ...

and

osteoblasts Osteoblasts (from the Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts functi ...

, and can cause indirect tissue damage.

Therapeutic uses

Collagenases have been approved for medical uses for: * treatment of Dupuytren's contracture and

Peyronie's disease Peyronie's disease (PD) is a benign, acquired penile connective tissue disease characterized by the occurrence of fibrotic plaques within the Tunica albuginea (penis), tunica albuginea — the dense elastic covering of the Corpora cavernosa of pe ...

( Xiaflex). *

wound healing Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue. In undamaged skin, the epidermis (surface, epithelial layer) and dermis (deeper, connective layer) form a protective barrier again ...

(Santyl) *

cellulite Cellulite () or gynoid lipodystrophy (GLD) is the herniation of subcutaneous fat within fibrous connective tissue that manifests as skin dimpling and nodularity, often on the pelvic region (specifically the buttocks), lower limbs, and abdomen. C ...

(Qwo)

The MEROPS M9 family

This group of metallopeptidases constitutes the

MEROPS MEROPS is an online database for peptidases (also known as proteases, proteinases and proteolytic enzymes) and their inhibitors. The classification scheme for peptidases was published by Rawlings & Barrett in 1993, and that for protein inhibito ...

peptidase family M9, subfamilies M9A and M9B (microbial collagenase, clan MA(E)). The

protein fold A protein superfamily is the largest grouping (clade) of proteins for which common ancestry can be inferred (see homology). Usually this common ancestry is inferred from structural alignment and mechanistic similarity, even if no sequence similar ...

of the peptidase

domain A domain is a geographic area controlled by a single person or organization. Domain may also refer to: Law and human geography * Demesne, in English common law and other Medieval European contexts, lands directly managed by their holder rather ...

for members of this family resembles that of thermolysin, the type example for clan MA and the predicted

active site 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, the ''binding s ...

residues for members of this family and thermolysin occur in the motif HEXXH.

Microbial A microorganism, or microbe, is an organism of microscopic size, which may exist in its single-celled form or as a colony of cells. The possible existence of unseen microbial life was suspected from antiquity, with an early attestation in ...

collagenases have been identified from

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

of both the ''Vibrio'' and ''Clostridium'' genera. Collagenase is used during bacterial attack to degrade the

barrier of the host during invasion. ''

Vibrio ''Vibrio'' is a genus of Gram-negative bacteria, which have a characteristic curved-rod (comma) shape, several species of which can cause foodborne infection or soft-tissue infection called Vibriosis. Infection is commonly associated with eati ...

'' bacteria are sometimes used in hospitals to remove dead tissue from burns and

ulcers An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing ...

. ''Clostridium histolyticum'' is a

pathogen In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a Germ theory of d ...

that causes gas gangrene; nevertheless, the isolated collagenase has been used to treat bed sores. Collagen

occurs at an in ''Vibrio'' bacteria and at bonds in ''Clostridium'' collagenases. Analysis of the

primary structure Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthe ...

of the

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

product from ''Clostridium perfringens'' has revealed that the

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

is produced with a stretch of 86 residues that contain a putative signal sequence. Within this stretch is found PLGP, an

amino acid sequence Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthe ...

typical of collagenase substrates. This

sequence In mathematics, a sequence is an enumerated collection of objects in which repetitions are allowed and order matters. Like a set, it contains members (also called ''elements'', or ''terms''). The number of elements (possibly infinite) is cal ...

may thus be implicated in self-processing of the collagenase.

Metalloproteases A metalloproteinase, or metalloprotease, is any protease enzyme whose catalytic mechanism involves a metal. An example is ADAM12 which plays a significant role in the fusion of muscle cells during embryo development, in a process known as myoge ...

are the most diverse of the seven main types of

protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalysis, catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products ...

, with more than 50 families identified to date. In these enzymes, a

divalent In chemistry, the valence (US spelling) or valency (British spelling) of an atom is a measure of its combining capacity with other atoms when it forms chemical compounds or molecules. Valence is generally understood to be the number of chemica ...

cation, usually zinc, activates the water molecule. The metal

ion An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...

is held in place by

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

ligands, usually three in number. The known metal

ligands In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's ...

are His, Glu, Asp, or Lys and at least one other residue is required for catalysis, which may play an electrophillic role. Of the known metalloproteases, around half contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site. The HEXXH motif is relatively common, but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often

valine Valine (symbol Val or V) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated −NH3+ form under biological conditions), an α- carboxylic acid group (which is in the deproton ...

or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a

hydrophobic In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...

residue.

Proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the p ...

is never found in this site, possibly because it would break the helical

structure A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...

adopted by this motif in metalloproteases.

Other uses

Collagenases may be used for tenderizing meat in a manner similar to widely used tenderizers

papain Papain, also known as papaya proteinase I, is a cysteine protease () enzyme present in papaya (''Carica papaya'') and mountain papaya (''Vasconcellea cundinamarcensis''). It is the namesake member of the papain-like protease family. It has wi ...

bromelain Bromelain is an enzyme extract derived from the plant stem, stems of pineapples, although it exists in all parts of the fresh plant and fruit. The extract has a history of folk medicine use. As a culinary ingredient, it may be used as a Meat tender ...

and

ficain Ficain also known as ficin, debricin, or higueroxyl delabarre () is a proteolytic enzyme extracted from the latex sap from the stems, leaves, and unripe fruit of the American wild fig tree ''Ficus insipida''. Ficain was originally called ficin, an ...

References

External links

* {{Portal bar, Biology, border=no EC 3.4.24 Protein families

Therapeutic uses

The MEROPS M9 family

Other uses

See also

References

External links