ArticleThe Journal of biological chemistry2015
Structural Basis for Ligand Recognition and Functional Selectivity at Angiotensin Receptor.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
96 citing papers in PubMed, 1 synthesis or guideline pooled it, 182 citations in OpenAlex.
- Antihypertensive Efficacy and Safety of Angiotensin Receptor Blockers (ARBs) with and without Inverse Agonism: A Systematic Review and Network Meta-analysis.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2026Pooled it
- Activation of the angiotensin II type I receptor by a nonpeptide agonist.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Preclinical Evaluation of the Antihypertensive Potential of Etcho (Pachycereus pecten-aboriginum) Fruit Juice using In Silico, In Vitro, and In Vivo Approaches.Plant foods for human nutrition (Dordrecht, Netherlands) · 2026Article
- Microbial Metabolite 4EPS Inhibits AT1R to Reduce Blood Pressure and Aortic Aneurysm Outcome.Hypertension (Dallas, Tex. : 1979) · 2026Article
- A roadmap to unveil the mechanism(s) of natural indole-derived molecules against NAFLD-derived HCC via systems pharmacology.Translational oncology · 2026Article
- Integrating Experimental and Computational Approaches to Cardioprotection: Vascular Reactivity, Molecular Docking, and ADMET Modeling ofInternational journal of molecular sciences · 2025Article
- Gating Mechanism for Biased Agonism at Angiotensin II Type 1 Receptors.Molecules (Basel, Switzerland) · 2025Article
- Epitope-directed selection of GPCR nanobody ligands with evolvable function.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Temporal complexity of LVV-hemorphin-7 allosterism at the angiotensin II type 1 receptor assessed using entropy-based approaches.Computational and structural biotechnology journal · 2025Article
- Antibodies expand the scope of angiotensin receptor pharmacology.Nature chemical biology · 2024Article
- Mechanical stress and anionic lipids synergistically stabilize an atypical structure of the angiotensin II type 1 receptor (AT1).PLoS computational biology · 2024Article
- Automated design of multi-target ligands by generative deep learning.Nature communications · 2024Article
- Phosphorylation patterns in the AT1R C-terminal tail specify distinct downstream signaling pathways.Science signaling · 2024Article
- G Protein-Coupled Receptor-Ligand Pose and Functional Class Prediction.International journal of molecular sciences · 2024Article
- Characterization of ACE inhibitory activity in Dioscorea alata cv and its implication as a natural antihypertensive extract.Journal of ethnopharmacology · 2024Article
- Insights Into the Role of Angiotensin-II ATHypertension (Dallas, Tex. : 1979) · 2024Review
- Complexation of the Antihypertensive Drug Olmesartan with Zn: In Vivo Antihypertensive and Cardiac Effects.Biological trace element research · 2024Article
- Unraveling allostery within the angiotensin II type 1 receptor for GαScience signaling · 2023Article
- Membrane mediated mechanical stimuli produces distinct active-like states in the AT1 receptor.Nature communications · 2023Article
- Structural insights into angiotensin receptor signaling modulation by balanced and biased agonists.The EMBO journal · 2023Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Angiotensin II type 1 receptor (AT1R) is the primary blood pressure regulator. AT1R blockers (ARBs) have been widely used in clinical settings as anti-hypertensive drugs and share a similar chemical scaffold, although even minor variations can lead to distinct therapeutic efficacies toward cardiovascular etiologies. The structural basis for AT1R modulation by different peptide and non-peptide ligands has remained elusive. Here, we report the crystal structure of the human AT1R in complex with an inverse agonist olmesartan (Benicar(TM)), a highly potent anti-hypertensive drug. Olmesartan is anchored to the receptor primarily by the residues Tyr-35(1.39), Trp-84(2.60), and Arg-167(ECL2), similar to the antagonist ZD7155, corroborating a common binding mode of different ARBs. Using docking simulations and site-directed mutagenesis, we identified specific interactions between AT1R and different ARBs, including olmesartan derivatives with inverse agonist, neutral antagonist, or agonist activities. We further observed that the mutation N111(3.35)A in the putative sodium-binding site affects binding of the endogenous peptide agonist angiotensin II but not the β-arrestin-biased peptide TRV120027.
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Registered trials
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.