Cellular and Molecular Life Sciences CMLS

, Volume 55, Issue 4, pp 639–652

Structural properties of matrix metalloproteinases

  • W. Bode
  • C. Fernandez-Catalan
  • H. Tschesche
  • F. Grams
  • H. Nagase
  • K. Maskos

DOI: 10.1007/s000180050320

Cite this article as:
Bode, W., Fernandez-Catalan, C., Tschesche, H. et al. CMLS, Cell. Mol. Life Sci. (1999) 55: 639. doi:10.1007/s000180050320

Abstract.

Matrix metalloproteinases (MMPs) are involved in extracellular matrix degradation. Their proteolytic activity must be precisely regulated by their endogenous protein inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). Disruption of this balance results in serious diseases such as arthritis, tumour growth and metastasis. Knowledge of the tertiary structures of the proteins involved is crucial for understanding their functional properties and interference with associated dysfunctions. Within the last few years, several three-dimensional MMP and MMP-TIMP structures became available, showing the domain organization, polypeptide fold and main specificity determinants. 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. A multitude of reviews surveying 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 was written to close the gap.

Key words. Matrix metalloproteinases (MMPs); tissue inhibitors of metalloproteinases (TIMPs); crystal structures; proteinases; drug design.

Copyright information

© Birkhäuser Verlag Basel, 1999

Authors and Affiliations

  • W. Bode
    • 1
  • C. Fernandez-Catalan
    • 1
  • H. Tschesche
    • 2
  • F. Grams
    • 1
  • H. Nagase
    • 3
  • K. Maskos
    • 1
  1. 1.Max-Planck-Institut für Biochemie, D-82152 Martinsried (Germany), Fax +49 89 8578 3516, e-mail: bode@biochem.mpg.deDE
  2. 2.Universität Bielefeld, Abteilung Biochemie I, D-33615 Bielefeld (Germany)DE
  3. 3.Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City (Kansas 66160, USA)US