Structural basis of matrix metalloproteinases and tissue inhibitors of metalloproteinases |
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Authors: | Klaus Maskos Wolfram Bode |
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Institution: | (1) Max-Planck-Institut für Biochemie, D-82152 Martinsried, Germany |
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Abstract: | The matrix metalloproteinases (MMPs) constitute a family of secreted/cell-surface-anchored multidomain zinc endopeptidases,
all of which exhibit a catalytic domain of a common metzincin-like topology, and which are involved in degradation of the
extracellular matrix but also in a number of other biologic processes. Normally, the proteolytic activity of the MMPs is precisely
regulated by their main endogenous protein inhibitors, in particular the tissue inhibitors of metalloproteinases (TIMPs).
Disruption of this balance results in serious diseases such as arthritis, tumor growth, and tumor metastasis, rendering the
MMPs attractive targets for inhibition therapy. Knowledge of their tertiary structures is crucial for a full understanding
of their functional properties and their associations with dysfunctions. Since the reports of the first atomic structures
of MMPs and TIMPs in 1994, considerable structural information has become available about both of these families of substances.
Many of the MMP structures have been determined as complexes with synthetic inhibitors, facilitating knowledge-based drug
design. This review focuses on the currently available 3D structural information about MMPs and TIMPs. |
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Keywords: | Proteinase matrix metalloproteinase tissue inhibitor of metalloproteinases |
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