Abstract
Matrix metalloproteinases are involved in many biological processes and in a large set of diseases. In the last twenty years the genetics, functions, and the structural features of this family of proteolytic enzymes have been investigated and a large number of synthetic inhibitors designed and tested. A better knowledge of the dynamical features of these proteins can be relevant not only to reveal new biological activities but also to design more specific and selective inhibitors. Here, we report the common and the distinct structural features of these proteins, the most recent published information on protein dynamics in matrix metalloproteinases and the recent results on the catalytic mechanism. The implications of the observed intra- and interdomain flexibility in matrix metalloproteinases for drug design have been analyzed and discussed.
Keywords: Matrix metalloproteinases, NMR, SAXS, protein dynamics, protein flexibility, protease inhibitors, structure based drug design
Current Pharmaceutical Design
Title: Intra- and Interdomain Flexibility in Matrix Metalloproteinases: Functional Aspects and Drug Design
Volume: 15 Issue: 31
Author(s): Ivano Bertini, Marco Fragai and Claudio Luchinat
Affiliation:
Keywords: Matrix metalloproteinases, NMR, SAXS, protein dynamics, protein flexibility, protease inhibitors, structure based drug design
Abstract: Matrix metalloproteinases are involved in many biological processes and in a large set of diseases. In the last twenty years the genetics, functions, and the structural features of this family of proteolytic enzymes have been investigated and a large number of synthetic inhibitors designed and tested. A better knowledge of the dynamical features of these proteins can be relevant not only to reveal new biological activities but also to design more specific and selective inhibitors. Here, we report the common and the distinct structural features of these proteins, the most recent published information on protein dynamics in matrix metalloproteinases and the recent results on the catalytic mechanism. The implications of the observed intra- and interdomain flexibility in matrix metalloproteinases for drug design have been analyzed and discussed.
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Cite this article as:
Bertini Ivano, Fragai Marco and Luchinat Claudio, Intra- and Interdomain Flexibility in Matrix Metalloproteinases: Functional Aspects and Drug Design, Current Pharmaceutical Design 2009; 15 (31) . https://dx.doi.org/10.2174/138161209789271852
DOI https://dx.doi.org/10.2174/138161209789271852 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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