Matrix metalloproteinase and other zinc-dependent metalloproteinase (MMP)

Matrix metalloproteinases (MMPs) and other zinc-dependent metalloproteinases, such as A Disintegrin and Metalloproteinases (ADAMs) and ADAMs with Thrombospondin motifs (ADAMTS), constitute a diverse group of endopeptidases that require a zinc ion at their catalytic site for enzymatic activity [1, 2, 10]. These enzymes are primary regulators of the extracellular matrix (ECM), facilitating the degradation of structural proteins like collagen, elastin, and fibronectin, which is essential for tissue remodeling, wound healing, and organogenesis [3, 4]. Beyond ECM degradation, they act as regulators of cell signaling by releasing membrane-bound cytokines, growth factors, and receptors, thereby modulating various physiological pathways [5]. In pathological states, overactive metalloproteinases contribute to tissue destruction in rheumatoid arthritis, promote tumor invasion and metastasis in cancer, and drive plaque instability in cardiovascular disease [6, 7]. Additionally, these enzymes are involved in the processing of the amyloid precursor protein, suggesting a role in neurodegenerative conditions like Alzheimer's disease [2, 6]. While early clinical trials of broad-spectrum MMP inhibitors like marimastat failed due to musculoskeletal toxicity and lack of efficacy, current research focuses on highly selective inhibitors and monoclonal antibodies to target specific isoforms involved in disease progression [8, 9].

Other names

MatrixinsZinc-dependent endopeptidasesADAMsADAMTSMatrix metallopeptidasesMetzincins

Chelation of the catalytic zinc ion, competitive inhibition of the active site, and allosteric modulation to prevent pro-enzyme activation or substrate binding [6, 8, 9].