Anita Dubey, Tanmay Sahu, Suchi Smita
The Bioinformatica Solutions, Lucknow (U.P), India.
Telomeres are repeated TTAGGG sequences that stop chromosome ends from behaving as random breaks. The up regulation of tankyrase1 protein encoded by TANKS gene (at Chromosome 8, NC_000008.10 (9413445..9639856)) in Homo sapiens, decreases the loading of Sheltrin complex (TRF1-TIN2-TPP1-POT1) on a chromosome end that is responsible for telomere protection and attenuates the impact of telomerase inhibitors by allowing access of telomerase activity. On the contrary, blockade of tankyrase 1 enhances the effect of telomerase inhibitors, tankyrase 1 leads to loss of DNA binding activity of telomerase by poly (ADP-ribosyl) ating TRF1 in sheltrin complex, resulting in degradation of Trf1complex (sheltrin) on telomeric region of DNA in cancerous cells, allowing telomerase binding on telomere, leading to the uncontrolled DNA replication. In this study tankyrase1 was taken as a target, PARP domain (PDB ID: 2RF5) of tankyrase1 is responsible for trf1’s poly (ADP-ribosyl)ation and degradation of sheltrin in cancerous cells, to inhibit activity of PARP domain docking is performed to find the inhibitors for PARP domain, docking predicted 13 different possible ligands interacting with 2RF5, out of these Acetoxy(4-aminophenyl)mercury is predicted best by analyzing energies and dock score.Read more…