Boehringer-Mannheim, TR-CS II, D-68305 Manhem, Germany.
Insights into MMP-TIMP Interactions
Article first published online: 6 FEB 2006
Annals of the New York Academy of Sciences
Volume 878, INHIBITION OF MATRIX METALLOPROTEINASES THERAPEUTIC APPLICATIONS pages 73–91, June 1999
How to Cite
BODE, W., FERNANDEZ-CATALAN, C., GRAMS, F., GOMIS-RÜTH, F.-X., NAGASE, H., TSCHESCHE, H. and MASKOS, K. (1999), Insights into MMP-TIMP Interactions. Annals of the New York Academy of Sciences, 878: 73–91. doi: 10.1111/j.1749-6632.1999.tb07675.x
- Issue published online: 6 FEB 2006
- Article first published online: 6 FEB 2006
ABSTRACT: The proteolytic activity of the matrix metalloproteinases (MMPs) involved in extracellular matrix degradation must be precisely regulated by their endogenous protein inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). Disruption of this balance can result in serious diseases such as arthritis and tumor growth and metastasis. Knowledge of the tertiary structures of the proteins involved in such processes is crucial for understanding their functional properties and to interfere with associated dysfunctions. Within the last few years, several three-dimensional structures have been determined showing the domain organization, the polypeptide fold, and the main specificity determinants of the MMPs. Complexes of the catalytic MMP domains with various synthetic inhibitors enabled the structure-based design and improvement of high-affinity ligands, which might be elaborated into drugs. Very recently, structural information also became available for some TIMP structures and MMP-TIMP complexes, and these new data elucidated important structural features that govern the enzyme-inhibitor interaction.