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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 ]


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


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.


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


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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