ArticleThe journal of physical chemistry. B2025
Synergistic Interplay of Stimulatory Cofactors in the Activation of Adenylyl Cyclase Isoform 1.
Article in The journal of physical chemistry. B, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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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.
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
1 citing paper in PubMed.
- Structural Studies of Fourth-Generation EGFR Inhibitors Reveal Insights into Selective T790M and C797S Targeting.ACS medicinal chemistry letters · 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
4 authors.
Funding
Abstract
Adenylyl Cyclase isoform 1 (AC1), responsible for synthesizing the signaling molecule cyclic adenosine monophosphate (cAMP), is key in synaptic plasticity, long-term chronic pain syndromes, osteosarcoma-associated pain, and drug abuse. The protein calmodulin (CaM) and the small molecule forskolin (Fsk) stimulate AC1 to form a catalytic site for ATP catalysis; however, molecular AC1 structural changes triggered by CaM and Fsk remain poorly understood. This study developed a computational model for AC1-cofactor complexes and used all-atom molecular dynamics (MD) simulations to determine how CaM and Fsk individually and jointly affect AC1 dynamics and assess whether they exhibit any synergistic effects. Four systems were investigated: AC1-No Partner, AC1-CaM, AC1-Fsk, and AC1-CaM-Fsk. Simulations revealed that individual and joint cofactor bindings induced unique structural changes within the regulatory C1b subdomain of AC1. CaM and Fsk binding result in a reduced cross section of the catalytic site, implying tighter binding for ATP. Notably, the results showed that the AC1-CaM-Fsk system exhibited unique features distinct from the AC1-CaM and AC1-Fsk systems, demonstrating synergistic effects of CaM and Fsk. Our understanding of AC1-cofactor interactions can guide future research toward modulating AC1 activity, potentially contributing to the development of novel treatments for AC1-associated diseases.
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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 Socratic graph.