collagenase1

Collagenase-1, also known as matrix metalloproteinase-1 (MMP-1), is a zinc-dependent endopeptidase in the matrix metalloproteinase family. It cleaves native fibrillar collagens and plays a key role in extracellular matrix remodeling. MMP-1 preferentially degrades collagen types I, II, and III, initiating collagen turnover in connective tissues.

The enzyme is synthesized as an inactive proenzyme with an N-terminal signal peptide for secretion, a prodomain that maintains latency via a cysteine switch, and a catalytic domain containing a zinc-binding active site. Activation occurs proteolytically, removing the pro-domain and enabling substrate binding and catalysis. The catalytic zinc is coordinated by histidine residues within the conserved HEXXHXXGXXH motif.

Expression and activity of MMP-1 are tightly regulated. Transcription is induced by cytokines, growth factors, and mechanical stress, while extracellular activity is controlled by tissue inhibitors of metalloproteinases (TIMPs), particularly TIMP-1, which limit substrate access.

Biological and clinical relevance: MMP-1 participates in normal physiological processes such as development, wound healing, and angiogenesis by allowing controlled remodeling of the extracellular matrix. It also contributes to pathological conditions including osteoarthritis, rheumatoid arthritis, fibrosis, and cancer invasion and metastasis, where degradation of collagen-rich matrices facilitates cell movement.

Research and therapeutic context: MMP-1 levels can be elevated in various diseases and have been explored as biomarkers. Broad-spectrum MMP inhibitors have encountered safety challenges in clinical development, prompting interest in more selective approaches to modulate MMP-1 activity. Related collagenases, such as MMP-8 and MMP-13, share substrate preferences but differ in tissue distribution and regulation.