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Peripheral Inhibition of Small C‐Terminal Domain Phosphatase 1 With Napthoquinone Analogs
Author(s) -
Rallabandi Harikrishna Reddy,
Lee Dongsun,
Sung Jinmo,
Kim Young Jun
Publication year - 2020
Publication title -
bulletin of the korean chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.237
H-Index - 59
ISSN - 1229-5949
DOI - 10.1002/bkcs.12051
Subject(s) - ctd , phosphatase , allosteric regulation , in silico , docking (animal) , chemistry , protein phosphatase 2 , biochemistry , computational biology , phosphorylation , biology , enzyme , gene , medicine , oceanography , nursing , geology
Small C‐terminal domain phosphatase 1(SCP1)'s biological function is significant in many cellular activities. Still, a recent study on neuroglioma cells emphasized the requirement of negative regulation of SCP1 in cancer invasion suppression. Due to the structural conservation of C‐terminal domain (CTD) phosphatases, we aimed to determine the peripherally targeting inhibitors, which reciprocally bind to an eccentric site on SCP1 using a multidisciplinary approach. From biochemical screening, we have identified two potential inhibitors, which showed twofold to threefold selectivity toward SCP1 compared to Dullard. Dullard was utilized as a negative control as it is a small CTD phosphatase that contains structural similarities to SCP1. Besides, from in silico approaches like protein–ligand docking and molecular dynamics analyses, we have successfully discovered two allosteric inhibitors of napthoquinone family compounds explicitly binding to the unique hydrophobic pocket of SCP1 from 1000 molecular dockings and 125 ns of dynamics simulation studies, respectively.