3D Structure of Adenylyl Cyclase

CPK Color Scheme
C O N P S



Adenylyl cyclase is an enzyme that catalyzes the conversion of ATP to cyclic AMP (cAMP). Nine mammalian isoforms have been identified, each expressed differently in various tissues of the body. Adenylyl cyclase is a dimer with a molecular weight of about 120,000 (Taussig, et. al, 1995). It is an integral membrane protein made up of two groups of six transmembrane units, each with a catalytic domain on the cytosylic side (Cooper, et. al, 1995). The molecule depicted here is the catalytic core of type II adenylyl cyclase, which is primarily expressed in the cerebellum. All adenylyl cyclases are activated by the hydrocarbon forskolin and the GTP-bound a-subunit of the stimulatory G protein; this form is also activated by the G protein By-subunit.

To explore the protein, click the buttons below:

To return to the original view of the adenylyl cyclase catalytic domain click here.

This view shows the two catalytic domain subunits (C1, green; C2,blue). The ligand forskolin is shown in red. Click here. Each monomer of the adenylyl cyclase molecule contributes one of the catalytic domains.

To see a closer view of the forskolin molecules click here. Two forskolin molecules bind in the ventral cavity between the two subunits and help stabalize the dimer (Zhang, et. al, 1997).

ATP shares part of its active site with one of the two forskolin sites (Tang, et. al, 1998). To view the catalytic site click here.

This view displays the binding site for the G protein a-subunit. It is the pocket on the top right of the C2 subunit (blue) (Yan, et. al, 1997). Click here.

References:

Cooper,D.M.F., Mons, N., and J.W. Karpen. (1995). Adenylyl cyclases and the interaction between calcium and cAMP signaling. Nature. 374, 421-424.

Tang, W. and J.H. Hurley. (1998). Catalytic mechanism and regulation of mammalian adenylyl cyclase. Molecular Pharmacology. 54, 231-240.

Taussig, R. and A.G. Gilman. (1995). Mammalian membrane-bound adenylyl cyclases. Journal of Biological Chemistry. 270, 1-4.

Yan, S.Z., Huang, Z.H., Rao, V.D., Hurley, J.H., and W.J. Tang. (1997). Three discrete regions of mammalian adenylyl cyclase form a site for G-sa activation. Journal of Biological Chemistry. 272, 18849-18854.

Zhang, G., Lui, Y., Ruoho, A.E., and J.H. Hurley. (1997). Structure of the adenylyl cyclase catalytic core. Nature. 386, 247-253.