Structural properties of matrix metalloproteinases

Matrix metalloproteinases (MMPs) are involved in extracellular matrix degra dation. Their proteolytic activity must. be precisely regulated by their en dogenous protein inhibitors, the tissue inhibitors of metalloproteinases (T IMPs). Disruption of this balance results in serious diseases such as arthr itis, tumour growth and metastasis. Knowledge of the tertiary structures of the proteins involved is crucial for understanding their functional proper ties and interference with associated dysfunctions. Within the last few yea rs, several three-dimensional MMP and MMP-TIMP structures became available, showing the domain organization, polypeptide fold and main specificity det erminants. Complexes of the catalytic MMP domains with various synthetic in hibitors enabled the structure-based design and improvement of high-affinit y ligands, which might be elaborated into drugs. A multitude of reviews sur veying work done on all aspects of MMPs have appeared in recent years, but none of them has focused on the three-dimensional structures. This review w as written to close the gap.