Metalloproteinase

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Introductions

Metalloproteases are characterized by the ability to retain quantitative metal ions and refer to proteases that contain metal ions in their active centers. A metalloprotease is any protease whose catalytic mechanism involves metals. Most metalloproteases require zinc, but some require cobalt. Metal ions are coordinated to proteins through three ligands. The ligands that coordinate the metal ions may vary depending on histidine, glutamate, aspartate, lysine, and arginine. The [clarification needed] fourth ligand is occupied by an unstable water molecule.

Functions

Metalloproteases always retain quantitative metal ions during the purification process, which cannot be removed by normal methods. However, if a chelating agent such as EDTA is present in the purification process, the metal ions are also lost and thus the enzyme activity is lost. Only by adding this ion again can restore its activity.

Ingredients

Some metalloproteases and the metal ions they contain are: trypsin (Ca), pancreatic rennet (Ca), carboxypeptidase (Zn), neutral protease (Zn), thermophilic bacterial protease (Ca, Zn), and collagenase (Ca, Zn). The optimum pH of these enzymes is generally between 7 and 9.

Metalloproteinases and Wound Healing

Metalloproteases are present in both acute and chronic wounds. They and their inhibitors play a key role in regulating the degradation and deposition of extracellular matrix, which is essential for wound re-epithelialization. Excessive protease activity leads to chronic non-healing wounds. the timely expression and activation of metalloproteases in wounds is essential for successful wound healing. the metalloproteases are divided into eight families and show extensive homology within these families. This homology led in part to the initial failure of metalloproteases inhibitors in clinical trials and to the development of alternative approaches to modulate metalloproteases activity. mouse models of metalloproteases knockout show altered wound healing responses, but these tend to be subtle phenotypic changes, suggesting overlap in metalloproteases substrate specificity and compensation between metalloproteases.

Regulation of Metalloproteinases Expression and Activity

The secretion and activity of metalloproteinases are highly regulated. In normal tissues, metalloproteinases is expressed at basal levels (if at all). When tissue remodeling is required (e.g. wound healing), metalloproteinases can be rapidly expressed and activated. A variety of different cell types express metalloproteinases within the skin (keratin-forming cells, fibroblasts, endothelial cells, and inflammatory cells such as monocytes, lymphocytes, and macrophages.) Metalloproteinases expression can be induced in response to a range of signals, including cytokines, hormones, and contact with other cell types or ECMs.

Metalloprotease Inhibitors

Metalloprotease inhibitors are found in many marine organisms, including fish, cephalopods, mollusks, algae, and bacteria.

Tissue Inhibitor of Metalloproteinases 3 (TIMP3)

Tissue inhibitor of metalloproteinases 3 (TIMP3) is unique among the four TIMPs because of its extracellular matrix (ECM) binding properties and wide range of inhibitory substrates, including matrix metalloproteinases (MMP), unlinkers and metalloproteinases (ADAM), as well as having a platelet-reactive protein motif (ADAMTS). In addition to its metalloprotease inhibitory function, TIMP3 can interact with proteins in the extracellular space, resulting in a variety of functions.