Structural Basis of the Matrix Metalloproteinases and Their Physiological Inhibitors, the Tissue Inhibitors of Metalloproteinases
-
Abstract
The matrix metalloproteinases (MMPs) constitute a family of multidomain zinc endopeptidases with a metzincin-like catalytic domain, which are involved in extracellular matrix degradation but also in a number of other important biological processes. Under healthy conditions, their proteolytic activity is precisely regulated by their main endogenous protein inhibitors, the tissue inhibitors of metalloproteinases. Disruption of this balance results in pathophysiological processes such as arthritis, tumor growth and 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 for rational drug design. Since the first appearance of atomic MMP structures in 1994, a large amount of structural information has become available on the catalytic domains of MMPs and their substrate specificity, interaction with synthetic inhibitors and the TIMPs, the domain organization, and on complex formation with other proteins. This review will outline our current structural knowledge of the MMPs and the TIMPs.
Copyright © 2003 by Walter de Gruyter GmbH & Co. KG
Articles in the same Issue
- Vito Turk – 30 Years of Research on Cysteine Proteases and Their Inhibitors
- Family C1 Cysteine Proteases: Biological Diversity or Redundancy?
- Molecular Regulation of Human Cathepsin B: Implication in Pathologies
- Caspases and Neuronal Development
- Structural Basis of the Matrix Metalloproteinases and Their Physiological Inhibitors, the Tissue Inhibitors of Metalloproteinases
- Managing Peptidases in the Genomic Era
- Insights into the Roles of Cathepsins in Antigen Processing and Presentation Revealed by Specific Inhibitors
- Cleavage Site Specificity of Cathepsin K toward Cartilage Proteoglycans and Protease Complex Formation
- Toward Computer-Based Cleavage Site Prediction of Cysteine Endopeptidases
- Isolation and Characterization of a Novel and Potent Inhibitor of Arg-Gingipain from Streptomyces sp. Strain FA-70
- Procongopain from Trypanosoma congolense Is Processed at Basic pH: An Unusual Feature among Cathepsin L-Like Cysteine Proteases
- Attenuated Kinin Release from Human Neutrophil Elastase-Pretreated Kininogens by Tissue and Plasma Kallikreins
- Effect of Plant Kunitz Inhibitors from Bauhinia bauhinioides and Bauhinia rufa on Pulmonary Edema Caused by Activated Neutrophils
- Revisiting Ubiquity and Tissue Specificity of Human Calpains
- The Calpastatin-Derived Calpain Inhibitor CP1B Reduces mRNA Expression of Matrix Metalloproteinase-2 and -9 and Invasion by Leukemic THP-1 Cells
- Heat Stress-Dependent DNA Binding of Arabidopsis Heat Shock Transcription Factor HSF1 to Heat Shock Gene Promoters in Arabidopsis Suspension Culture Cells in vivo
- T47-D Cells and Type V Collagen: A Model for the Study of Apoptotic Gene Expression by Breast Cancer Cells
Articles in the same Issue
- Vito Turk – 30 Years of Research on Cysteine Proteases and Their Inhibitors
- Family C1 Cysteine Proteases: Biological Diversity or Redundancy?
- Molecular Regulation of Human Cathepsin B: Implication in Pathologies
- Caspases and Neuronal Development
- Structural Basis of the Matrix Metalloproteinases and Their Physiological Inhibitors, the Tissue Inhibitors of Metalloproteinases
- Managing Peptidases in the Genomic Era
- Insights into the Roles of Cathepsins in Antigen Processing and Presentation Revealed by Specific Inhibitors
- Cleavage Site Specificity of Cathepsin K toward Cartilage Proteoglycans and Protease Complex Formation
- Toward Computer-Based Cleavage Site Prediction of Cysteine Endopeptidases
- Isolation and Characterization of a Novel and Potent Inhibitor of Arg-Gingipain from Streptomyces sp. Strain FA-70
- Procongopain from Trypanosoma congolense Is Processed at Basic pH: An Unusual Feature among Cathepsin L-Like Cysteine Proteases
- Attenuated Kinin Release from Human Neutrophil Elastase-Pretreated Kininogens by Tissue and Plasma Kallikreins
- Effect of Plant Kunitz Inhibitors from Bauhinia bauhinioides and Bauhinia rufa on Pulmonary Edema Caused by Activated Neutrophils
- Revisiting Ubiquity and Tissue Specificity of Human Calpains
- The Calpastatin-Derived Calpain Inhibitor CP1B Reduces mRNA Expression of Matrix Metalloproteinase-2 and -9 and Invasion by Leukemic THP-1 Cells
- Heat Stress-Dependent DNA Binding of Arabidopsis Heat Shock Transcription Factor HSF1 to Heat Shock Gene Promoters in Arabidopsis Suspension Culture Cells in vivo
- T47-D Cells and Type V Collagen: A Model for the Study of Apoptotic Gene Expression by Breast Cancer Cells
