Structural Basis of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases
- 1 January 2003
- journal article
- review article
- Published by Springer Science and Business Media LLC in Molecular Biotechnology
- Vol. 25 (3), 241-266
- https://doi.org/10.1385/mb:25:3:241
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.Keywords
This publication has 99 references indexed in Scilit:
- Crystal structure of the stromelysin-3 (MMP-11) catalytic domain complexed with a phosphinic inhibitor mimicking the transition-stateJournal of Molecular Biology, 2001
- Matrix metalloproteinasesEuropean Journal Of Cancer, 2000
- Post-translational Proteolytic Processing of Procollagen C-terminal Proteinase Enhancer Releases a Metalloproteinase InhibitorJournal of Biological Chemistry, 2000
- Cloning and Characterization of Human MMP-23, a New Matrix Metalloproteinase Predominantly Expressed in Reproductive Tissues and Lacking Conserved Domains in Other Family MembersJournal of Biological Chemistry, 1999
- The Helping Hand of Collagenase-3 (MMP-13): 2.7 Å Crystal Structure of its C-terminal Haemopexin-like DomainJournal of Molecular Biology, 1996
- Computational sequence analysis of matrix metalloproteinasesProtein Journal, 1996
- The C‐terminal (haemopexin‐like) domain structure of human gelatinase A (MMP2): structural implications for its functionFEBS Letters, 1996
- Mutation of the Active Site Glutamic Acid of Human Gelatinase A: Effects on Latency, Catalysis, and the Binding of Tissue Inhibitor of Metalloproteinases-1Biochemistry, 1994
- SETOR: Hardware-lighted three-dimensional solid model representations of macromoleculesJournal of Molecular Graphics, 1993
- On the size of the active site in proteases. I. PapainBiochemical and Biophysical Research Communications, 1967