Matrix Metalloproteinases

Matrix metalloproteinases (MMPs) are a family of extracellular zinc-dependent neutral endopeptidases that collectively play an important role in embryonal development, tissue regeneration, and wound repair. They come from a subclass of proteolytic enzymes that break proteins down into fragments able to be regenerated. The MMPs thus process the proteins in the structural area in which our cells live, contributing to the breakdown of collagen and elastins in our skin as well as numerous other extracellular matrix proteins.

MMPs thus serve a number of functions throughout our bodies, aside from breaking down structural proteins. They are involved in the cleavage of cell surface receptors, and play a major role in cell behaviors such as proliferation, migration, differentiation and host defense. They assist in the second phase of wound healing, creating pathways for the movement of immune cells to infected areas, and have a large role in regenerating the skin matrix.

Not all MMPs have major effects on the skin (see table below). There are a number of MMP enzymes, each with a different target and preferred type of protein. MMP enzymes that deal with structural skin matrix proteins, namely elastin and collagen (types I, II and, to a lesser degree, V, VI and XII- see article on Collagen) should thus be the primary focus for individuals seeking to slow the breakdown of these proteins in their skin. Collagen and elastin are primarily responsible for the health and beauty of our skin

The smoothness, tightness and youthful appearance of our skin are largely results of the condition and health of our skin matrix, which is the product of a complex cycle of protein growth and breakdown. When the cycle slows or stops, skin imperfections occur. MMP enzymes are responsible for cell regeneration. Excessive decomposition of the skin matrix due to raised levels of MMP is a common problem, and MMP levels tend to increase as we age. Inflation, irritation, and external factors such as sun exposure and smoking tend to speed up the aging process, and thus MMP production and the breakdown of proteins in our skin.

Research has proven that bringing elevated MMP levels back to those seen in young people should be a core component of a successful skin rejuvenation regime for older individuals.

Classification of Matrix Metalloproteinases

Taken From Matrix_metalloproteinase (Wikipedia, the free encyclopedia)

Evolutionary

Use of bioinformatic methods to compare the primary sequences of the MMPs suggest the following evolutionary groupings of the MMPs:

MMP-19
MMPs 11, 14, 15, 16 and 17
MMP-2 and MMP-9
all the other MMPs

Analysis of the catalytic domains in isolation suggests that the catalytic domains evolved further once the major groups had differentiated, as is also indicated by the substrate specificities of the enzymes.

Functional

The most commonly used groupings (by researchers in MMP biology) are based partly on historical assessment of the substrate specificity of the MMP and partly on the cellular localization of the MMP. These groups are the collagenases, the gelatinases, the stromelysins, and the membrane type MMPs (MT-MMPs).

The collagenases are capable of degrading triple-helical fibrillar collagens into distinctive 3/4 and 1/4 fragments. These collagens are the major components of bone and cartilage, and MMPs are the only known mammalian enzymes capable of degrading them. Traditionally, the collagenases are #1, #8, #13, and #18. In addition, #14 has also been shown to cleave fibrillar collagen, and more controversially there is evidence that #2 is capable of collagenolysis. In MeSH, the current list of collegenases includes #1, #2, #8, #9, and #13. #14 is present in MeSH but not listed as a collegenase, while #18 is absent from MeSH.
The main substrates of the gelatinases are type IV collagen and gelatin, and these enzymes are distinguished by the presence of an additional domain inserted into the catalytic domain. This gelatin-binding region is positioned immediately before the zinc binding motif, and forms a separate folding unit which does not disrupt the structure of the catalytic domain. The gelatinases are #2 and #9.
The stromelysins display a broad ability to cleave extracellular matrix proteins but are unable to cleave the triple-helical fibrillar collagens. The three canonical members of this group are #3, #10, and #11.
All six membrane type MMPs (#14, #15, #16, #17, #24, and #25) have a furin cleavage site in the pro-peptide, which is a feature also shared by #11.

However, it is becoming increasingly clear that these divisions are somewhat artificial as there are a number of MMPs that do not fit into any of the traditional groups.

Genes

Gene	Name	Location	Description
MMP1	Interstitial collagenase	secreted
MMP2	Gelatinase-A, 72 kDa gelatinase	secreted
MMP3	Stromelysin 1	secreted
MMP7	Matrilysin, PUMP 1	secreted	membrane associated through binding to cholesterol sulfate in cell membranes
MMP8	Neutrophil collagenase	secreted
MMP9	Gelatinase-B, 92 kDa gelatinase	secreted
MMP10	Stromelysin 2	secreted
MMP11	Stromelysin 3	secreted	MMP-11 shows more similarity to the MT-MMPs, is convertase-activatable and is secreted therefore usually associated to convertase-activatable MMPs.
MMP12	Macrophage metalloelastase	secreted
MMP13	Collagenase 3	secreted
MMP14	MT1-MMP	membrane-associated	type-I transmembrane MMP
MMP15	MT2-MMP	membrane-associated	type-I transmembrane MMP
MMP16	MT3-MMP	membrane-associated	type-I transmembrane MMP
MMP17	MT4-MMP	membrane-associated	glycosyl phosphatidylinositol-attached
MMP18	Collagenase 4, xcol4, xenopus collagenase	-	No known human orthologue
MMP19	RASI-1, occasionally referred to as stromelysin-4	-
MMP20	Enamelysin	secreted
MMP21	X-MMP	secreted
MMP23A	CA-MMP	membrane-associated	type-II transmembrane cysteine array
MMP23B	-	membrane-associated	type-II transmembrane cysteine array
MMP24	MT5-MMP	membrane-associated	type-I transmembrane MMP
MMP25	MT6-MMP	membrane-associated	glycosyl phosphatidylinositol-attached
MMP26	Matrilysin-2, endometase	-
MMP27	MMP-22, C-MMP	-
MMP28	Epilysin	secreted	Discovered in 2001 and given its name due to have been discovered in human keratinocytes. Unlike other MMPs this enzyme is constitutivley expressed in many tissues (Highly expressed in testis and at lower levels in lung, heart, brain, colon, intestine, placenta, salivary glands, uterus, skin). A threonine replaces proline in its cysteine switch (PRCGVTD).

Matrix metalloproteinases combine with the metal binding protein, metallothionine; thus helping in metal binding mechanism.