ArticleChemMedChem2014
Crystal structure of human soluble adenylate cyclase reveals a distinct, highly flexible allosteric bicarbonate binding pocket.
Article in ChemMedChem, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Soluble adenylyl cyclase in nonmammalian sperm is directly controlled by pH, not by HCOProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Updating the Mechanism of Bicarbonate (HCOInternational journal of molecular sciences · 2025Article
- Rosmarinic Acid Present inPlants (Basel, Switzerland) · 2024Article
- Article
- Scaffold Hopping and Optimization of Small Molecule Soluble Adenyl Cyclase Inhibitors Led by Free Energy Perturbation.Journal of chemical information and modeling · 2023Article
- Discovery of TDI-10229: A Potent and Orally Bioavailable Inhibitor of Soluble Adenylyl Cyclase (sAC, ADCY10).ACS medicinal chemistry letters · 2021Article
- Preclinical contraceptive development for men and women.Biology of reproduction · 2020Review
- Optimization of lead compounds into on-demand, nonhormonal contraceptives: leveraging a public-private drug discovery institute collaboration†.Biology of reproduction · 2020Article
- Molecular basis for GTP recognition by light-activated guanylate cyclase RhGC.The FEBS journal · 2020Article
- The Regulatory Role of Key Metabolites in the Control of Cell Signaling.Biomolecules · 2020Review
- Synergistic mutations in soluble guanylyl cyclase (sGC) reveal a key role for interfacial regions in the sGC activation mechanism.The Journal of biological chemistry · 2019Article
- Increased Levels of cAMP by the Calcium-Dependent Activation of Soluble Adenylyl Cyclase inCells · 2019Article
- Pharmacological modulation of the COPharmacology & therapeutics · 2018Review
- Structure-guided design and functional characterization of an artificial red light-regulated guanylate/adenylate cyclase for optogenetic applications.The Journal of biological chemistry · 2018Article
- Proton Transport Chains in Glucose Metabolism: Mind the Proton.Frontiers in neuroscience · 2018Review
- International Union of Basic and Clinical Pharmacology. CI. Structures and Small Molecule Modulators of Mammalian Adenylyl Cyclases.Pharmacological reviews · 2017Review
- Discovery of LRE1 as a specific and allosteric inhibitor of soluble adenylyl cyclase.Nature chemical biology · 2016Article
- Bithionol Potently Inhibits Human Soluble Adenylyl Cyclase through Binding to the Allosteric Activator Site.The Journal of biological chemistry · 2016Article
- Detection of secondary binding sites in proteins using fragment screening.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Soluble adenylyl cyclase in health and disease.Biochimica et biophysica acta · 2014Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Soluble adenylate cyclases catalyse the synthesis of the second messenger cAMP through the cyclisation of ATP and are the only known enzymes to be directly activated by bicarbonate. Here, we report the first crystal structure of the human enzyme that reveals a pseudosymmetrical arrangement of two catalytic domains to produce a single competent active site and a novel discrete bicarbonate binding pocket. Crystal structures of the apo protein, the protein in complex with α,β-methylene adenosine 5'-triphosphate (AMPCPP) and calcium, with the allosteric activator bicarbonate, and also with a number of inhibitors identified using fragment screening, all show a flexible active site that undergoes significant conformational changes on binding of ligands. The resulting nanomolar-potent inhibitors that were developed bind at both the substrate binding pocket and the allosteric site, and can be used as chemical probes to further elucidate the function of this protein.
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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.