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Update of human and mouse matrix metalloproteinase families
Brian C Jackson1, Daniel W Nebert, Vasilis Vasiliou
1Molecular Toxicology and Environmental Health Sciences Program, Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO 80045, USA.
Abstract:
Matrix metalloproteinases (MMPs) are a family of zinc proteases that degrade most of the components of the extracellular matrix (ECM). MMPs also have a number of non-traditional roles in processing factors related to cell growth/proliferation, inflammation and more. There are 23 human MMPs and 23 mouse MMPs, most of which share orthology among most vertebrates; other examples have been found in invertebrates and plants. MMPs are named in order of discovery, but also have been grouped by domain structure or by phylogenetic analysis. MMPs are multi-domain proteins which generally contain a signal sequence; propeptide (which keeps the protein inactive until cleaved); catalytic domain; and a hemopexin-like domain (which provides substrate specificity). MMPs are thought to play a role in many disease states, including arthritis, vascular disease, lung injury, wound repair, cancer and various neurodegenerative disorders. Although there has been much clinical interest in MMP inhibitors (MMPIs), few trials have been successful - often due to the broad nature of inhibition and the complex role of different MMPs in a given disease state.
Insights
Matrix metalloproteinases (MMPs) are zinc proteases that degrade extracellular matrix and have roles in cell growth and inflammation. MMP inhibitors have shown limited success due to the complexity of MMP roles in disease.
Area of Science:
- Biochemistry
- Molecular Biology
- Enzymology
Background:
- Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteases.
- They are crucial for degrading extracellular matrix (ECM) components.
- MMPs also regulate cell growth, proliferation, and inflammation.
Purpose of the Study:
- To provide an overview of Matrix metalloproteinases (MMPs).
- To discuss their structure, function, and role in various diseases.
- To highlight the challenges in developing MMP inhibitors (MMPIs).
Main Methods:
- Review of existing literature on MMPs.
- Analysis of MMP domain structure and phylogenetic relationships.
- Discussion of clinical trial outcomes for MMPIs.
Main Results:
- There are 23 human and 23 mouse MMPs, with conserved orthologs across vertebrates.
- MMPs possess multi-domain structures including signal sequence, propeptide, catalytic, and hemopexin-like domains.
- MMPs are implicated in diseases like arthritis, cancer, and neurodegeneration.
Conclusions:
- MMPs are essential enzymes with diverse roles beyond ECM degradation.
- Their involvement in numerous pathologies underscores their clinical significance.
- Developing effective and specific MMP inhibitors remains a challenge due to MMP complexity.
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