Site-Directed Mutagenesis and Time-Resolved Fluorescence Spectroscopy Reveal That Two Hydrogen-Bonded Carboxylic Side Chains Are Essential for GPR68 Proton Sensing and G Protein Binding.

Bhav Kapur, Eva Martin, Ana-Nicoleta Bondar, Michael Schuler, Esther Schmidt, Herbert Nar, Gisela Schnapp

Abstract read

In one paragraph

Article in ACS pharmacology & translational science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed

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1 · What the graph read from it

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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.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Bhav KapurDepartment of Medicinal Chemistry, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer str. 65, 88397 Biberach an der Riss, Germany.ORCID https://orcid.org/0000-0002-7828-5793

Eva MartinDepartment of Drug Discovery Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer str. 65, 88397 Biberach an der Riss, Germany.

Ana-Nicoleta BondarFaculty of Physics, University of Bucharest, Atomiştilor 405, 077125 Măgurele, Romania.ORCID https://orcid.org/0000-0003-2636-9773

Michael SchulerDepartment of Drug Discovery Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer str. 65, 88397 Biberach an der Riss, Germany.

Esther SchmidtDepartment of Drug Discovery Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer str. 65, 88397 Biberach an der Riss, Germany.

Herbert NarDepartment of Medicinal Chemistry, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer str. 65, 88397 Biberach an der Riss, Germany.ORCID https://orcid.org/0000-0002-3878-6964

Gisela SchnappDepartment of Medicinal Chemistry, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer str. 65, 88397 Biberach an der Riss, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

GPR68 is a pH-sensing G protein-coupled receptor widely expressed throughout the body. It has been implicated in various diseases, including neurodegeneration, chronic inflammation, and cancer, emphasizing its role in pathophysiology. The identities of the structural elements essential for pH sensing have been controversial, as experiments and sequence analyses have been interpreted to suggest that an extracellular histidine cluster or, by contrast, an internal carboxylic triad, senses the extracellular pH. Recent molecular simulations and hydrogen-bond network analyses suggested instead a unifying mechanism whereby the extracellular histidine residues and the internal carboxylic triad couple to each other via a protonation-sensitive hydrogen-bond network that includes a fourth internal carboxylic group, E103

Indexed as

GPR68G protein-coupled receptorsHomogeneous time-resolved fluorescenceImmunofluorescenceProton sensingWater-mediated hydrogen-bond network

Identifiers

PMID41262562

DOI10.1021/acsptsci.5c00516

PMCPMC12624488

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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.