title: Molecular Characterization and In-Silico Analysis of the Tissue Inhibitor of Metalloproteinases-3 (TIMP-3) Gene of Canine Mammary Tumor.
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.
authors.affiliation: Division of Biochemistry, Indian Veterinary Research Institute, Izatnagar, Bareilly-243122, Uttar Pradesh, India.
authors.forename: Pavan Kumar
authors.initials: PK
authors.lastname: Yadav
authors.affiliation: Department of Molecular Biology and Ecology of Plant, Tel Aviv University, Tel Aviv 689978. Israel.
authors.forename: Brijesh Singh
authors.initials: BS
authors.lastname: Yadav
authors.affiliation: Division of Medicine, Indian Veterinary Research Institute, Izatnagar, Bareilly-243 122, Uttar Pradesh, India.
authors.forename: Padma Nibash
authors.initials: PN
authors.lastname: Panigrahi
authors.affiliation: Genome Diversity Center, The Institute of Evolution, University of Haifa, Haifa. Israel.
authors.forename: Vijay
authors.initials: V
authors.lastname: Tripathi
authors.affiliation: Department of Biochemistry & Molecular Biology, Tel Aviv University, Tel Aviv-689978. Israel.
authors.forename: Navaneet
authors.initials: N
authors.lastname: Chaturvedi
authors.affiliation: Division of Biochemistry, Indian Veterinary Research Institute, Izatnagar, Bareilly-243122, Uttar Pradesh, India.
authors.forename: Meena
authors.initials: M
authors.lastname: Kataria
mesh_terms: D000818:Animals; D003001:Cloning, Molecular; D003198:Computer Simulation; D004285:Dogs; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D015674:Mammary Neoplasms, Animal / Q000201:enzymology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D017422:Sequence Analysis, DNA; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D019717:Tissue Inhibitor of Metalloproteinase-3; D020782:Matrix Metalloproteinases
keywords: Matrixmetalloproteinases; docking; molecular dynamic simulation; tissue inhibitors of metalloproteinases