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Updated: Aug 17, 2026

Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications
Published on: January 27, 2014
The adenylyl and guanylyl cyclase superfamily
1Laboratory of Molecular Biology National Institute of Diabetes, Digestive and Kidney Diseases National Institutes of Health Bethesda MD 20892-0580 USA. jh8e@nih.gov
Abstract:
New structures solved in 1997 revealed that the adenylyl cyclase core consists of a pair of catalytic domains arranged in a wreath. Homologous catalytic domains are arranged in diverse adenylyl and guanylyl cyclases as symmetric homodimers or pseudosymmetric heterodimers. The kinship of the adenylyl and guanylyl cyclases has been confirmed by the structure-based interconversion of their nucleotide specificities. Catalysis is activated when two metal-binding aspartate residues on one domain are juxtaposed with a key aspargine-arginine pair on the other. Allosteric activators of mammalian adenylyl cyclase, forskolin and the stimulatory G protein alpha subunit, promote the catalytically optimal juxtaposition of the two domains.
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