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Science 278 (5345): 1907-1916

Copyright © 1997 by the American Association for the Advancement of Science

Crystal Structure of the Catalytic Domains of Adenylyl Cyclase in a Complex with Gsalpha·GTPgamma S

John J. G. Tesmer, Roger K. Sunahara, Alfred G. Gilman, Stephen R. Sprang

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 .

J. J. G. Tesmer and S. R. Sprang are at the Howard Hughes Medical Institute and the Department of Biochemistry, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9050, USA. R. K. Sunahara and A. G. Gilman are in the Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9041, USA.

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PNAS 101, 3242-3247
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Adenylyl Cyclase G Is Activated by an Intramolecular Osmosensor.
S. Saran and P. Schaap (2004)
Mol. Biol. Cell 15, 1479-1486
   Abstract »    Full Text »    PDF »
G Protein Signaling: Insights from New Structures.
A. M. Preininger and H. E. Hamm (2004)
Sci. STKE 2004, re3
   Abstract »    Full Text »    PDF »
Differential Gene Expression in Auristatin PHE-Treated Cryptococcus neoformans.
T. Woyke, M. E. Berens, D. B. Hoelzinger, G. R. Pettit, G. Winkelmann, and R. K. Pettit (2004)
Antimicrob. Agents Chemother. 48, 561-567
   Abstract »    Full Text »    PDF »
Allosteric determinants in guanine nucleotide-binding proteins.
M. E. Hatley, S. W. Lockless, S. K. Gibson, A. G. Gilman, and R. Ranganathan (2003)
PNAS 100, 14445-14450
   Abstract »    Full Text »    PDF »
A Defined Subset of Adenylyl Cyclases Is Regulated by Bicarbonate Ion.
M. J. Cann, A. Hammer, J. Zhou, and T. Kanacher (2003)
J. Biol. Chem. 278, 35033-35038
   Abstract »    Full Text »    PDF »
Regulation of Nitric Oxide-Sensitive Guanylyl Cyclase.
A. Friebe and D. Koesling (2003)
Circ. Res. 93, 96-105
   Abstract »    Full Text »    PDF »
Tissue Transglutaminase Directly Regulates Adenylyl Cyclase Resulting in Enhanced cAMP-response Element-binding Protein (CREB) Activation.
J. Tucholski and G. V. W. Johnson (2003)
J. Biol. Chem. 278, 26838-26843
   Abstract »    Full Text »    PDF »
Multiple Splice Variants Encode a Novel Adenylyl Cyclase of Possible Plastid Origin Expressed in the Sexual Stage of the Malaria Parasite Plasmodium falciparum.
D. K. Muhia, C. A. Swales, U. Eckstein-Ludwig, S. Saran, S. D. Polley, J. M. Kelly, P. Schaap, S. Krishna, and D. A. Baker (2003)
J. Biol. Chem. 278, 22014-22022
   Abstract »    Full Text »    PDF »
Kinetic Properties of "Soluble" Adenylyl Cyclase. SYNERGISM BETWEEN CALCIUM AND BICARBONATE.
T. N. Litvin, M. Kamenetsky, A. Zarifyan, J. Buck, and L. R. Levin (2003)
J. Biol. Chem. 278, 15922-15926
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2'(3')-O-(N-Methylanthraniloyl)-substituted GTP Analogs: A Novel Class of Potent Competitive Adenylyl Cyclase Inhibitors.
A. Gille and R. Seifert (2003)
J. Biol. Chem. 278, 12672-12679
   Abstract »    Full Text »    PDF »
Structural view of a fungal toxin acting on a 14-3-3 regulatory complex.
M. Wurtele, C. Jelich-Ottmann, A. Wittinghofer, and C. Oecking (2003)
EMBO J. 22, 987-994
   Abstract »    Full Text »    PDF »
Small Ligands Modulating the Activity of Mammalian Adenylyl Cyclases: A Novel Mode of Inhibition by Calmidazolium.
A. Haunso, J. Simpson, and F. A. Antoni (2003)
Mol. Pharmacol. 63, 624-631
   Abstract »    Full Text »    PDF »
GAF Domains: Cyclic Nucleotides Come Full Circle.
J. H. Hurley (2003)
Sci. STKE 2003, pe1
   Abstract »    Full Text »    PDF »
Coordinate regulation of membrane cAMP by Ca2+-inhibited adenylyl cyclase and phosphodiesterase activities.
J. R. Creighton, N. Masada, D. M. F. Cooper, and T. Stevens (2003)
Am J Physiol Lung Cell Mol Physiol 284, L100-L107
   Abstract »    Full Text »    PDF »
Deducing the Origin of Soluble Adenylyl Cyclase, a Gene Lost in Multiple Lineages.
J. Roelofs and P. J. M. Van Haastert (2002)
Mol. Biol. Evol. 19, 2239-2246
   Abstract »    Full Text »    PDF »
Distinct Interactions of GTP, UTP, and CTP with Gs Proteins.
A. Gille, H.-Y. Liu, S. R. Sprang, and R. Seifert (2002)
J. Biol. Chem. 277, 34434-34442
   Abstract »    Full Text »    PDF »
Mechanism of G{alpha}i-mediated Inhibition of Type V Adenylyl Cyclase.
C. W. Dessauer, M. Chen-Goodspeed, and J. Chen (2002)
J. Biol. Chem. 277, 28823-28829
   Abstract »    Full Text »    PDF »

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