Evidence map›Paper›PMID 31531399›Full record

ArticleCommunications biology2019

Development of R7BP inhibitors through cross-linking coupled mass spectrometry and integrated modeling.

Poorni R Adikaram, Jian-Hua Zhang, Claire M Kittock, Mritunjay Pandey, Sergio A Hassan, Nicole G Lue, Guanghui Wang, Marjan Gucek, William F Simonds

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.1field-weighted citation impact, top 52% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Poorni R Adikaram *1Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bldg. 10/Rm 8C-101, Bethesda, MD 20892 USA.
Jian-Hua Zhang *1Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bldg. 10/Rm 8C-101, Bethesda, MD 20892 USA.
Claire M Kittock1Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bldg. 10/Rm 8C-101, Bethesda, MD 20892 USA.
Mritunjay Pandey1Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bldg. 10/Rm 8C-101, Bethesda, MD 20892 USA.
Sergio A Hassan2Center for Molecular Modeling, Center for Information Technology, Bldg. 12/Rm 2049, Bethesda, MD 20892 USA.
Nicole G Lue1Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bldg. 10/Rm 8C-101, Bethesda, MD 20892 USA.
Guanghui Wang3Proteomics Core, National Heart Lung and Blood Institute, National Institutes of Health, Bldg. 10/Rm 8C-103A, Bethesda, MD 20892 USA.
Marjan Gucek3Proteomics Core, National Heart Lung and Blood Institute, National Institutes of Health, Bldg. 10/Rm 8C-103A, Bethesda, MD 20892 USA.
William F Simonds1Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bldg. 10/Rm 8C-101, Bethesda, MD 20892 USA.ORCID 0000-0001-7806-706X
National Institute of Diabetes and Digestive and Kidney Diseases · USNational Institutes of Health · USCenter for Information Technology · US

Funding

Mechanism of G Protein Beta5/ R7-RGS Protein/ R7BP Complex Signal TransductionZIADK043304 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI SIMONDS, WILLIAM F · 2009 to 2025
$14.8M
Intramural NIH HHS ZIA DK043304
6 · The paper itself

Abstract

Protein-protein interaction (PPI) networks are known to be valuable targets for therapeutic intervention; yet the development of PPI modulators as next-generation drugs to target specific vertices, edges, and hubs has been impeded by the lack of structural information of many of the proteins and complexes involved. Building on recent advancements in cross-linking mass spectrometry (XL-MS), we describe an effective approach to obtain relevant structural data on R7BP, a master regulator of itch sensation, and its interfaces with other proteins in its network. This approach integrates XL-MS with a variety of modeling techniques to successfully develop antibody inhibitors of the R7BP and RGS7/Gβ5 duplex interaction. Binding and inhibitory efficiency are studied by surface plasmon resonance spectroscopy and through an R7BP-derived dominant negative construct. This approach may have broader applications as a tool to facilitate the development of PPI modulators in the absence of crystal structures or when structural information is limited.

Indexed as

Drug DesignModels, MolecularAmino Acid SequenceAntibodies, MonoclonalBinding SitesDrug DiscoveryHumansLigandsMolecular ConformationMolecular Docking SimulationMolecular Dynamics SimulationProtein BindingRGS ProteinsStructure-Activity RelationshipSurface Plasmon ResonanceAntibodies, MonoclonalLigandsRGS7BP protein, humanRGS ProteinsGTP-binding protein regulatorsMolecular neuroscienceProtein structure predictions

Identifiers

PMID31531399
PMCPMC6744478
OpenAlexW2972560904

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.