ArticleCommunications chemistry2025
Coevolving residues distant from the ligand binding site are involved in GAF domain function.
Article in Communications chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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.
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.
Who cites it
2 citing papers in PubMed.
- A P3' methionine-to-phenylalanine substitution in the NSP6-7 substrate peptide alters SARS-CoV-2 MThe Journal of biological chemistry · 2026Article
- E50A Mutation Increases the Bioluminescence Activity of picALuc.Biosensors · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ligand binding to GAF domains regulates the activity of associated catalytic domains in various proteins, such as the cGMP-hydrolyzing catalytic domain of phosphodiesterase 5 (PDE5) activated by cGMP binding to GAFa domain. However, the specific residues involved and the mechanism of GAF domain function remain unclear. Here, we combine computational and experimental approaches to demonstrate that two highly coevolving residues, L267 and F295, distant from the ligand binding site, play a critical role in GAF domain allostery. Statistical Coupling Analysis (SCA) of GAF domain sequences identified these residues, and molecular dynamics (MD) simulations of both apo and holo forms of wild-type and mutant (L267A, F295A) PDE5 GAFa domains revealed significant changes in structural dynamics and cGMP interaction. Mutational incorporation into a Bioluminescence Resonance Energy Transfer (BRET)-based biosensors, which detects ligand-induced conformational changes, showed altered GAF domain conformation and increased EC
Identifiers
What OpenQuestion holds
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.