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
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
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.