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Title |
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Structural insights into the binding of MMP9 inhibitors |
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Authors |
Arpit Tandon1*, Siddharth Sinha2 |
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Affiliation |
1Amity Institute of Biotechnology, Amity University Lucknow Campus, Gomti Nagar, Lucknow 226010, India; 2ACS BioInformatics, Biotech Park, Janki Puram, Lucknow 226021, India |
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Article Type |
Hypothesis
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Date |
Received September 14, 2010; Accepted December 02, 2010; Published January 22, 2011 |
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Abstract |
Matrix Metalloproteinase are family of enzymes responsible for degradation of extracellular matrix. MMP9 (gelatinase B) is one of the common matrix metalloproteinase that is associated with tissue destruction in a number of disease states such as rheumatoid arthiritis, fibrotic lung disease, dilated cardiomyopathy, as well as cancer invasion and metastasis. Recent study demonstrates that increased expression of MMP9 results in augmentation of myopathy with increased inflammation and fibernecrosis. Previous studies do not provide any conclusive information related to structural specificity of MMP9 inhibitors towards its active site, but with the availability of experimental structures it is now possible to study the structural specificity of MMP9 inhibitors. In light of availability of this information, we have applied docking and molecular dynamics approach to study the binding of inhibitors to the active site of MMP9. Three categories of inhibitor consisting of sulfonamide hydroxamate, thioester, and carboxylic moieties as zinc binding groups (ZBG) were chosen in the present study. Our docking results demonstrate that thioester based zinc binding group gives favourable docking scores as compared to other two groups. Molecular Dynamics simulations further reveal that tight binding conformation for thioester group has high specificity for MMP9 active site. Our study provides valuable insights on inhibitor specificity of MMP9 which provides valuable hints for future design of potent inhibitors and drugs. |
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Citation |
Tandon & Sinha, Bioinformation 5(8): 310-314 (2010) |
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Edited by |
Asad U KhAN
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ISSN |
0973-2063
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Publisher |
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License |
This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License. |