Evidence map›Paper›PMID 42185275›Full record

ArticleNature communications2026

Molecular mechanisms for subtype selectivity of kinin receptors' antagonists.

Meng Xia, Aleksey Raskovalov, My V T Nguyen, Shiliu Mei, Donggyun Kim, Jayden Salve, Vsevolod Katritch, Vadim Cherezov, Haitao Zhang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 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

9 authors.

Meng Xia *Research Center for Clinical Pharmacy, Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, State Key Laboratory of Advanced Drug Delivery and Release Systems, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0009-0005-8476-3252
Aleksey Raskovalov *Bridge Institute, USC Michelson Center for Convergent Biosciences, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-1207-5312
My V T Nguyen *Bridge Institute, USC Michelson Center for Convergent Biosciences, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-5567-9378
Shiliu Mei *Research Center for Clinical Pharmacy, Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, State Key Laboratory of Advanced Drug Delivery and Release Systems, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
Donggyun KimBridge Institute, USC Michelson Center for Convergent Biosciences, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-2861-3397
Jayden SalveBridge Institute, USC Michelson Center for Convergent Biosciences, University of Southern California, Los Angeles, CA, USA.
Vsevolod KatritchBridge Institute, USC Michelson Center for Convergent Biosciences, University of Southern California, Los Angeles, CA, USA. katritch@usc.edu.ORCID http://orcid.org/0000-0003-3883-4505
Vadim CherezovBridge Institute, USC Michelson Center for Convergent Biosciences, University of Southern California, Los Angeles, CA, USA. cherezov@usc.edu.ORCID http://orcid.org/0000-0002-5265-3914
Haitao ZhangResearch Center for Clinical Pharmacy, Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, State Key Laboratory of Advanced Drug Delivery and Release Systems, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China. haitaozhang@zju.edu.cn.ORCID http://orcid.org/0000-0003-4879-2951

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81722044, 91753115, 21778049, 81861148018Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation) Z23C050004
6 · The paper itself

Abstract

The kinin receptors B1R and B2R act as key regulators within the kallikrein-kinin system, mediating vasodilation, inflammation, and pain. Antagonists targeting these receptors have shown therapeutic potential in the treatment of angioedema, pancreatitis, and asthma. However, the molecular mechanisms underlying subtype selectivity of kinin receptors' antagonists remain unclear. Here we report three cryo-electron microscopy (cryo-EM) structures of B1R in complex with the peptide antagonist R715 and small-molecule antagonist ELN441958, as well as B2R in complex with small-molecule antagonist Win64338. Together with functional assays and molecular docking, these structures unveil the molecular basis of antagonist binding modes in kinin receptors. Three non-conserved residues at the bottom of the ligand binding pocket are identified to confer the antagonist selectivity to B1R and B2R. Furthermore, our results reveal a shared mechanism for antagonism in both B1R and B2R, wherein the antagonist binding restricts the conformational changes of the toggle switch tryptophan residue. Collectively, these insights lay the foundation for the structure-based design of selective antagonists targeting B1R and B2R.

Indexed as

Bradykinin B1 Receptor AntagonistsBradykinin B2 Receptor AntagonistsReceptor, Bradykinin B1Receptor, Bradykinin B2AnimalsBinding SitesCryoelectron MicroscopyHumansLigandsMolecular Docking SimulationProtein BindingProtein ConformationBradykinin B1 Receptor AntagonistsBradykinin B2 Receptor AntagonistsLigandsReceptor, Bradykinin B1Receptor, Bradykinin B2

Identifiers

PMID42185275
PMCPMC13385906

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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.