Receptor based virtual screening of potential novel inhibitors of tigar [TP53 (tumour protein 53)-induced glycolysis and apoptosis regulator.

Autor: Poyya J; Department of Biochemistry, Mangalore University, Jana Kaveri Post Graduate Centre Chikka Aluvara, Kodagu 571 232, India., Kumar DJ; Department of Biotechnology, Sir M. Visvesvaraya Institute of Technology, Bangalore, India., Nagendra HG; Department of Biotechnology, Sir M. Visvesvaraya Institute of Technology, Bangalore, India., Dinesh B; Department of Biochemistry, Mangalore University, Jana Kaveri Post Graduate Centre Chikka Aluvara, Kodagu 571 232, India., Aditya Rao SJ; Plant Cell Biotechnology Department, CSIR-Central Food Technological Research Institute, Mysore 570017, Karnataka, India; Department of Biotechnology, Sahyadri Science College, Kuvempu University, Shivamogga 570003, Karnataka, India., Joshi CG; Department of Biochemistry, Mangalore University, Jana Kaveri Post Graduate Centre Chikka Aluvara, Kodagu 571 232, India. Electronic address: josheejoshee@gmail.com.
Jazyk: angličtina
Zdroj: Medical hypotheses [Med Hypotheses] 2021 Nov; Vol. 156, pp. 110683. Date of Electronic Publication: 2021 Sep 20.
DOI: 10.1016/j.mehy.2021.110683
Abstrakt: TP53 (tumor protein 53)-induced glycolysis and apoptosis regulator (TIGAR) belongs to the phosphatases family of proteins that modulates the level of reactive oxygen species in tumor cells. This protein plays a vital role as a negative regulator of glycolysis, thus lowering ROS levels in the cells, which helps the cancerous cells to resist programmed cell death. Besides, TIGAR also mediates the DNA damage repair in cancer cells by increasing tumor cell survival. In the current study, we have screened natural products that compete with the substrate to bind to the active site of TIGAR. Extra precision and MMGBSA scoring function were used to screen the lead molecules. Five compounds were considered as lead molecules with 2-(2-(3,4-dihydroxy phenyl)-3,5-dihydroxy-8-(4-hydroxyphenyl)-4-oxo-4H-furo[2,3-h]chromen-9-yl) acetic acid(DDFA) as a top lead with a docking score of -9.428, and -53.16 MMGBSA, bind to the positively charged amino acids present in the active site. Further, the molecular dynamics simulation studies indicated the structural stability attained by TIGAR protein upon the binding of DDFA, suggesting it to be a potent inhibitor of TIGAR, and could be employed as an anticancer drug during combinational therapy.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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