In Silico Identification of Potential Inhibitor Against a Fungal Histone Deacetylase, RPD3 from Magnaporthe Oryzae

Histone acetylation and deacetylation play an essential role in the epigenetic regulation of gene expression. Histone deacetylases (HDAC) are a group of zinc-binding metalloenzymes that catalyze the removal of acetyl moieties from lysine residues from histone tails. These enzymes are well known for...

Full description

Saved in:
Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2019-05, Vol.24 (11), p.2075
Main Authors: Shanmugam, Gnanendra, Kim, Taehyeon, Jeon, Junhyun
Format: Article
Language:English
Subjects:
Acetylation
Acids
Binding sites
Biological effects
Deacetylation
Enzymes
Epigenetics
Eukaryotes
Fungi
Gene expression
Histone deacetylase
histone deacetylases
Histones
Hydrogen bonds
Infections
Inhibitors
Lysine
Magnaporthe oryzae
Molecular docking
MoRPD3
Proteins
Rice blast
Therapeutic targets
Trichostatin A
virtual screening
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Histone acetylation and deacetylation play an essential role in the epigenetic regulation of gene expression. Histone deacetylases (HDAC) are a group of zinc-binding metalloenzymes that catalyze the removal of acetyl moieties from lysine residues from histone tails. These enzymes are well known for their wide spread biological effects in eukaryotes. In rice blast fungus, , MoRPD3 (an ortholog of ) was shown to be required for growth and development. Thus in this study, the class I HDAC, MoRpd3 is considered as a potential drug target, and its 3D structure was modelled and validated. Based on the model, a total of 1880 compounds were virtually screened (molecular docking) against MoRpd3 and the activities of the compounds were assessed by docking scores. The in silico screening suggested that [2-[[4-(2-methoxyethyl) phenoxy] methyl] phenyl] boronic acid (-8.7 kcal/mol) and [4-[[4-(2-methoxyethyl) phenoxy] methyl] phenyl] boronic acid (-8.5 kcal/mol) are effective in comparison to trichostatin A (-7.9 kcal/mol), a well-known general HDAC inhibitor. The in vitro studies for inhibition of appressorium formation by [2-[[4-(2-methoxyethyl) phenoxy] methyl] phenyl] boronic acid has resulted in the maximum inhibition at lower concentrations (1 μM), while the trichostatin A exhibited similar levels of inhibition at 1.5 μM. These findings thus suggest that 3D quantitative structure activity relationship studies on [2-[[4-(2-methoxyethyl) phenoxy] methyl] phenyl] boronic acid compound can further guide the design of more potential and specific HDAC inhibitors.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules24112075