UMB Data Catalog

A project of the Health Sciences and Human Services Library
UMB Dataset

Small molecules inhibitors of the heterogeneous ribonuclear protein A18 (hnRNP A18): a regulator of protein translation and an immune checkpoint

UID: 219
Author(s): Eduardo Solano-Gonzalez, Katherine M. Coburn, Wenbo Yu, Gerald M. Wilson, Elmar Nurmemmedov...
* Corresponding Author
Description
Researchers utilized SILCS-based techniques to map the functional group requirements of hnRNP A18, aiming to create a pharmacophore for virtual screening. Data was obtained using the crystal structure of the hnRNP A18 RRM domain and various software tools. These simulations generated 3D functional group probability distributions of organic solutes, forming the basis for pharmacophore models. Virtual screening of compound databases was then conducted using these pharmacophore models. Experimental assays, including PAMPA, NMR spectroscopy, RNA binding activity assays, fluorescence anisotropy, and cellular thermal shift assays, were performed on selected compounds. Finally, in vivo studies on tumor growth inhibition in mice models complemented the in vitro findings.
Subject of Study
Subject Domain
RNA-Binding Proteins / chemistry
RNA-Binding Proteins/antagonists & inhibitors
Keywords
Antineoplastic Agents / therapeutic use
Cancer Therapy

Access

Restrictions
Unrestricted access
Instructions
Datatables available in the Supplementary Materials. Backbone chemical shift assignments for the RRM domain of hnRNP A18 are deposited in the Biological Magnetic Resonance Database.
Access via Supplementary materials

datatables

Access via BRMB

Backbone chemical shift assignments for the RRM domain of hnRNP A18.
Accession #: 28117

Associated Publications
Solano-Gonzalez E, Coburn KM, Yu W, Wilson GM, Nurmemmedov E, Kesari S, Chang ET, MacKerell AD, Weber DJ, Carrier F. Small molecules inhibitors of the heterogeneous ribonuclear protein A18 (hnRNP A18): a regulator of protein translation and an immune checkpoint. Nucleic Acids Res. 2021 Feb 22;49(3):1235-1246.
Coburn K, Melville Z, Aligholizadeh E, Roth BM, Varney KM, Carrier F, Pozharski E, Weber DJ. Crystal structure of the human heterogeneous ribonucleoprotein A18 RNA-recognition motif. Acta Crystallogr F Struct Biol Commun. 2017 Apr 1;73(Pt 4):209-214.
Data Type
Genomic
Biochemical
Equipment Used
Amicon Ultra Centrifugal Filter

A device for concentrating and purifying biomolecules by centrifugation-based filtration.

ApoTox-Glo Triplex Assay

A multiplexed assay for assessing cell viability, cytotoxicity, and apoptosis simultaneously.

Beacon 2000 Fluorescence Polarization System

Equipment for measuring the binding interactions between molecules based on changes in fluorescence polarization.

Bio-Rad Protein Assay

A method and associated reagents used for quantifying protein concentrations in biological samples.

Bruker Avance 800 US2 NMR spectrometer

A high-field NMR instrument capable of providing detailed structural information about molecules in solution.

CAT ELISA

An enzyme-linked immunosorbent assay (ELISA) for detecting catalase protein levels.

His-tagged purification kit

A kit designed for the purification of recombinant proteins with a histidine tag.

HisTrap FF column

A chromatography column used for affinity purification of proteins containing a histidine tag.

LI-COR C-Digit Blot Scanner

A scanner designed for quantitative analysis of Western blots and other protein or nucleic acid detection assays.

LightShift Chemiluminescent RNA EMSA kit

A kit for detecting RNA-protein interactions using electrophoretic mobility shift assays (EMSA) coupled with chemiluminescent detection.

Magna RIP RNA-Binding Protein Immunoprecipitation Kit

A kit for isolating RNA-protein complexes using immunoprecipitation, commonly used in RNA research.

PAMPA Evolution instrument

A tool for predicting passive absorption across biological membranes, commonly used in drug discovery.

Xenogen IVIS optical imager

An device for non-invasive in vivo imaging of bioluminescent and fluorescent signals in small animals.

Software Used
GraphPad Prism

A tool for analyzing and visualizing complex biological data, particularly in the fields of genomics and proteomics.

GROMACS

A versatile package used for molecular dynamics simulations, particularly in bioinformatics and computational chemistry.

Living Image 3.0

Imaging software designed for analyzing and quantifying data from in vivo imaging experiments, often used in preclinical research.

MOE program

A comprehensive software suite for molecular modeling, simulation, and drug discovery applications.

NMRPipe

Software for processing and analyzing nuclear magnetic resonance (NMR) spectroscopy data, commonly used in structural biology.

Pharmer

A computational tool utilized in drug discovery for virtual screening and pharmacophore modeling.

Reduce software

A tool for simplifying and condensing complex data or processes within software systems.

SILCS

Computational methods utilizing Site Identification by Ligand Competitive Saturation (SILCS) to predict ligand binding sites on proteins.

Study Type
Interventional
Dataset Format(s)
XLS, str
Data Collection Instruments
Boltzmann transformation
SILCS-Pharm protocol
four-parameter logistic equation
Dataset Size
177K, 13 KB
Grant Support
Cigarette Restitution Fund Program/Maryland. Department of Health
RO1CA177981-01/National Institutes of Health (U.S.)
R35 GM131710/National Institutes of Health (U.S.)
Center for Biomolecular Therapeutics fund/University of Maryland Computer-Aided Drug Design Center
I.P. Fund/Center for Maryland Advanced Ventures Life Sciences