Limits...
Structural insights into the binding of MMP9 inhibitors.

Tandon A, Sinha S - Bioinformation (2011)

Bottom Line: 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.Our docking results demonstrate that thioester based zinc binding group gives favourable docking scores as compared to other two groups.Our study provides valuable insights on inhibitor specificity of MMP9 which provides valuable hints for future design of potent inhibitors and drugs.

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus

Docked conformations of Inhibitors in Red (Autodock) and Green (Flexidock) with respect to crystal structure ligand in blue. (a) Carboxylic acid ZBG (b) Sulfonamide Hydroxamate ZBG (c) Thio ester based ZBG
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3046033&req=5

Figure 1: Docked conformations of Inhibitors in Red (Autodock) and Green (Flexidock) with respect to crystal structure ligand in blue. (a) Carboxylic acid ZBG (b) Sulfonamide Hydroxamate ZBG (c) Thio ester based ZBG


Structural insights into the binding of MMP9 inhibitors.

Tandon A, Sinha S - Bioinformation (2011)

Docked conformations of Inhibitors in Red (Autodock) and Green (Flexidock) with respect to crystal structure ligand in blue. (a) Carboxylic acid ZBG (b) Sulfonamide Hydroxamate ZBG (c) Thio ester based ZBG
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3046033&req=5

Figure 1: Docked conformations of Inhibitors in Red (Autodock) and Green (Flexidock) with respect to crystal structure ligand in blue. (a) Carboxylic acid ZBG (b) Sulfonamide Hydroxamate ZBG (c) Thio ester based ZBG
Bottom Line: 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.Our docking results demonstrate that thioester based zinc binding group gives favourable docking scores as compared to other two groups.Our study provides valuable insights on inhibitor specificity of MMP9 which provides valuable hints for future design of potent inhibitors and drugs.

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus