Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsalpha.GTPgammaS

Science. 1997 Dec 12;278(5345):1907-16. doi: 10.1126/science.278.5345.1907.


The crystal structure of a soluble, catalytically active form of adenylyl cyclase in a complex with its stimulatory heterotrimeric G protein alpha subunit (Gsalpha) and forskolin was determined to a resolution of 2.3 angstroms. When P-site inhibitors were soaked into native crystals of the complex, the active site of adenylyl cyclase was located and structural elements important for substrate recognition and catalysis were identified. On the basis of these and other structures, a molecular mechanism is proposed for the activation of adenylyl cyclase by Gsalpha.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adenylyl Cyclase Inhibitors
  • Adenylyl Cyclases / chemistry*
  • Adenylyl Cyclases / metabolism
  • Amino Acid Sequence
  • Binding Sites
  • Catalysis
  • Colforsin / metabolism
  • Crystallization
  • Crystallography, X-Ray
  • Dimerization
  • Enzyme Activation
  • GTP-Binding Protein alpha Subunits, Gs / chemistry*
  • GTP-Binding Protein alpha Subunits, Gs / metabolism
  • Guanosine 5'-O-(3-Thiotriphosphate) / chemistry*
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Ligands
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Phosphorylation
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary


  • Adenylyl Cyclase Inhibitors
  • Ligands
  • Colforsin
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Adenosine Triphosphate
  • GTP-Binding Protein alpha Subunits, Gs
  • Adenylyl Cyclases

Associated data

  • PDB/1AZS