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Molecular Characterization and In-Silico Analysis of the Tissue Inhibitor of Metalloproteinases-3 (TIMP-3) Gene of Canine Mammary Tumor

[ Vol. 20 , Issue. 6 ]

Author(s):

Pavan Kumar Yadav, Brijesh Singh Yadav, Padma Nibash Panigrahi, Vijay Tripathi, Navaneet Chaturvedi and Meena Kataria   Pages 539 - 546 ( 8 )

Abstract:


Background: Mammary tumors are the second most common tumors (after skin tumors) in female dogs (Canis lupus familiaris). Tissue Inhibitor of Metlloproteinases-3 (TIMP-3) is a matrix associated endogenous inhibitor of Matrix Metalloproteinases (MMPs). Cancer metastasis occurs as a result of imbalance between MMPs and TIMPs. TIMP-3 is involved significantly in regulation of MMPs as well as progression of canine mammary tumor.

Objective: The present study was conducted to identify the structural and functional relationship between TIMP-3 and MMP which can aid in identifying the role of these proteins in canine mammary tumor.

Methods: Molecular characterization of TIMP-3 protein was done by molecular biology techniques such as gene cloning and sequencing. The homology based model of TIMP-3 protein was created and verified with a variety of available computational techniques as well as molecular dynamics simulation.

Results: The results indicated that predicted TIMP-3 protein structure of Canis lupus familiaris was reliable and more stable. The docking of TIMP-3 protein with MMP-2 and MMP-9 represents conformational structure of these two proteins which interact with each other but if misled canresult in the progression of tumor in canine.

Conclusions: The three dimensional structure of TIMP-3 was generated and its interactions with MMP-2 and MMP-9, demonstrates the role of key binding residues. Until now, no structural details were available for canine TIMP-3 proteins, hence this study will broaden the horizon towards understanding the structural and functional aspects of this proteins in canine.

Keywords:

Matrixmetalloproteinases, tissue inhibitors of metalloproteinases, molecular dynamic simulation, docking.

Affiliation:

Division of Biochemistry, Indian Veterinary Research Institute, Izatnagar, Bareilly-243122, Uttar Pradesh, Department of Molecular Biology and Ecology of Plant, Tel Aviv University, Tel Aviv 689978, Division of Medicine, Indian Veterinary Research Institute, Izatnagar, Bareilly-243 122, Uttar Pradesh, Genome Diversity Center, The Institute of Evolution, University of Haifa, Haifa, Department of Biochemistry & Molecular Biology, Tel Aviv University, Tel Aviv-689978, Division of Biochemistry, Indian Veterinary Research Institute, Izatnagar, Bareilly-243122, Uttar Pradesh



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