CRYSTAL-STRUCTURE OF THE CATALYTIC DOMAINS OF ADENYLYL-CYCLASE IN A COMPLEX WITH G(S-ALPHA).GTP-GAMMA-S

The crystal structure of a soluble, catalytically active form of adeny lyl cyclase in a complex with its stimulatory heterotrimeric G protein alpha subunit (G(S alpha)) and forskolin was determined to a resoluti on of 2.3 angstroms. When P-site inhibitors were soaked into native cr ystals of the complex, the active site of adenylyl cyclase was located and structural elements important for substrate recognition and catal ysis were identified. On the basis of these and other structures, a mo lecular mechanism is proposed for the activation of adenylyl cyclase b y G(S alpha).