Evidence map›Paper›PMID 42125920›Full record

ArticleActa crystallographica. Section D, Structural biology2026

Peptide binding at the gasdermin D exosite reveals the structural basis for targeting the site.

Renjing Wang, Thu Ho, Aimie Ogawa, Kartika Widjaja, Zachary Brown, Song Yang, Pei Huo, Michael C Gregory, Aman Singh, Senthil Perumal and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta crystallographica. Section D, Structural biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

16 authors.

Renjing WangProtein and Structural Chemistry, Merck & Co., Inc, 213 East Grand Avenue, South San Francisco, CA 94080, USA.ORCID 0009-0003-3257-5140
Thu HoProtein and Structural Chemistry, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, USA.
Aimie OgawaQuantitative Biosciences, Merck & Co., Inc., 213 East Grand Avenue, South San Francisco, CA 94080, USA.
Kartika WidjajaDiscovery Biology, Merck & Co., Inc., 213 East Grand Avenue, South San Francisco, CA 94080, USA.
Zachary BrownDiscovery Chemistry, Merck & Co., Inc., 126 East Lincoln Avenue, Rahway, NJ 07065, USA.
Song YangModeling and Informatics, Merck & Co., Inc., 213 East Grand Avenue, South San Francisco, CA 94080, USA.
Pei HuoDiscovery Chemistry, Merck & Co., Inc., 213 East Grand Avenue, South San Francisco, CA 94080, USA.
Michael C GregoryQuantitative Biosciences, Merck & Co., Inc., 213 East Grand Avenue, South San Francisco, CA 94080, USA.
Aman SinghQuantitative Biosciences, Merck & Co., Inc., 213 East Grand Avenue, South San Francisco, CA 94080, USA.
Senthil PerumalQuantitative Biosciences, Merck & Co., Inc., 213 East Grand Avenue, South San Francisco, CA 94080, USA.ORCID 0009-0003-2458-061X
Songnian LinDiscovery Chemistry, Merck & Co., Inc., 126 East Lincoln Avenue, Rahway, NJ 07065, USA.
Alan C ChengModeling and Informatics, Merck & Co., Inc., 213 East Grand Avenue, South San Francisco, CA 94080, USA.
Lindsay S GarrentonQuantitative Biosciences, Merck & Co., Inc., 213 East Grand Avenue, South San Francisco, CA 94080, USA.
James MuDiscovery Biology, Merck & Co., Inc., 213 East Grand Avenue, South San Francisco, CA 94080, USA.
Anthony OgawaDiscovery Chemistry, Merck & Co., Inc., 213 East Grand Avenue, South San Francisco, CA 94080, USA.
Jill E ChrencikProtein and Structural Chemistry, Merck & Co., Inc, 213 East Grand Avenue, South San Francisco, CA 94080, USA.ORCID 0009-0005-6322-0478

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Gasdermin D (GSDMD) has been identified as a critical component of the inflammasome, an important intracellular signaling multi-protein complex. Abnormal activation of GSDMD has been linked to a variety of inflammatory diseases, including non-alcoholic steatohepatitis, inflammatory bowel disease and COVID-19, and has been linked to potential pathogenesis of septic shock. While small molecules have been identified to inhibit N-terminal domain (NTD) pore formation and membrane translocation, further clinical application of these molecules is currently limited due to narrow specificity. Here, we report a peptide from a structure-based computational screen that selectively inhibits caspase-dependent cleavage of GSDMD. We have determined the structure of the GSDMD-peptide complex, indicating that peptide binding is facilitated by negatively charged residues from the peptide and the hydrophobic exosite of the protein, inhibiting caspase binding and activation. The experimental data suggest the potential to target the exosite for therapeutic intervention.

Indexed as

Intracellular Signaling Peptides and ProteinsNeoplasm ProteinsPeptidesPhosphate-Binding ProteinsApoptosis Regulatory ProteinsBinding SitesCrystallography, X-RayGasderminsHumansModels, MolecularProtein BindingApoptosis Regulatory ProteinsGasderminsGSDMD protein, humanIntracellular Signaling Peptides and ProteinsNeoplasm ProteinsPeptidesPhosphate-Binding Proteinscyclic peptidesdruggabilityexositegasdermin Dinhibitionstructure-based drug design

Identifiers

PMID42125920
PMCPMC13224929

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Registered trials

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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 OpenQuestion graph.