Structure of the adenylyl cyclase catalytic core

• Published in: Nature (London) Vol. 386; no. 6622; pp. 247 - 253
• Main Authors: Zhang, Gongyi, Liu, Yu, Ruoho, Arnold E, Hurley, James H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 20-03-1997; Nature Publishing Group
• Subjects: Adenylyl Cyclases - chemistry; Adenylyl Cyclases - metabolism; Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Animals; Binding Sites; Biological and medical sciences; Catalysis; Catalysts; Colforsin - metabolism; Crystalline structure; Crystallography, X-Ray; Enzyme Activation; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Lyases; Mammals; Models, Molecular; Molecular biology; Molecular biophysics; Molecular Sequence Data; Protein Binding; Protein Conformation; Protein Folding; Proteins; Rats; Rodents; Structure in molecular biology; Catalytic subunit; Adenylate cyclase; Vertebrata; Mammalia; Molecular structure; Enzyme; Quaternary structure; Phosphorus-oxygen lyases; Lyases; Structural analysis; Crystalline structure
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/386247a0

Mammalian adenylyl cyclases contain two conserved regions, C1 and C2, which are responsible for forskolin- and G-protein-stimulated catalysis. The structure of the C2 catalytic region of type II rat adenylyl cyclase has an alpha/beta class fold in a wreath-like dimer, which has a central cleft. Two forskolin molecules bind in hydrophobic pockets at the ends of cleft. The central part of the cleft is lined by charged residues implicated in ATP binding. Forskolin appears to activate adenylyl cyclase by promoting the assembly of the active dimer and by direct interaction within the catalytic cleft. Other adenylyl cyclase regulators act at the dimer interface or on a flexible C-terminal region.