In-Silico Evidence for Binding of Pentacyclic Triterpenoids to Keap1-Nrf2 Protein-Protein Binding Site.

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In-Silico Evidence for Binding of Pentacyclic Triterpenoids to Keap1-Nrf2 Protein-Protein Binding Site.

Comb Chem High Throughput Screen. 2016 Dec 14;

Authors: Kamble SM, Patel HM, Goyal SN, Noolvi MN, Mahajan UB, Ojha S, Patil CR

Abstract
Kelch like ECH-associated protein 1 (Keap1) and Nuclear factor-E2 related factor 2 (Nrf2) binding is a key step in the ubiquitination and degradation of Nrf2. The compounds inhibiting this binding exert antioxidant actions. Naturally occurring pentacyclic triterpenoids (PTs) and their synthetic derivatives are projected as activators of Nrf2 signalling. The 16-mer Nrf2 peptide binding site on Keap-1 (PDB: 2 FLU) is proposed to be the prospective target for a tetracyclic triterpenoid called gedunine. In present study, seventy seven PTs of natural and synthetic origin are screened for Nrf2 stimulatory activity using online PASS (Prediction of Activity Spectrum of Substances) software followed by in-silico molecular docking against 16-mer Nrf2 peptide binding site on Keap-1. This virtual screening reveals that Nrf2 stimulatory PTs dock on the 16-mer peptide binding site on Keap-1 and may exert their biological activities by interfering with the Keap-1 and Nrf2 binding.

PMID: 28024463 [PubMed - as supplied by publisher]

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