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Science 11 August 1995:
Vol. 269. no. 5225, pp. 807 - 813
DOI: 10.1126/science.7638597
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Articles

Science, Vol 269, Issue 5225, 807-813
Copyright © 1995 by American Association for the Advancement of Science

articles

Regulatory subunit of protein kinase A: structure of deletion mutant with cAMP binding domains

Y Su, WR Dostmann, FW Herberg, K Durick, NH Xuong, L Ten Eyck, SS Taylor, and KI Varughese

Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093-0654, USA.

In the molecular scheme of living organisms, adenosine 3',5'-monophosphate (cyclic AMP or cAMP) has been a universal second messenger. In eukaryotic cells, the primary receptors for cAMP are the regulatory subunits of cAMP-dependent protein kinase. The crystal structure of a 1-91 deletion mutant of the type I alpha regulatory subunit was refined to 2.8 A resolution. Each of the two tandem cAMP binding domains provides an extensive network of hydrogen bonds that buries the cyclic phosphate and the ribose between two beta strands that are linked by a short alpha helix. Each adenine base stacks against an aromatic ring that lies outside the beta barrel. This structure provides a molecular basis for understanding how cAMP binds cooperatively to its receptor protein, thus mediating activation of the kinase.


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J. Biol. Chem. 273, 22833-22840
   Abstract »    Full Text »    PDF »
Divergent cAMP Signaling Pathways Regulate Growth and Pathogenesis in the Rice Blast Fungus Magnaporthe grisea.
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   Abstract »    Full Text »
Activation by Autophosphorylation or cGMP Binding Produces a Similar Apparent Conformational Change in cGMP-dependent Protein Kinase.
D.-M. Chu, S. H. Francis, J. W. Thomas, E. A. Maksymovitch, M. Fosler, and J. D. Corbin (1998)
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   Abstract »    Full Text »    PDF »
Potential Roles of Conserved Amino Acids in the Catalytic Domain of the cGMP-binding cGMP-specific Phosphodiesterase (PDE5).
I. V. Turko, S. H. Francis, and J. D. Corbin (1998)
J. Biol. Chem. 273, 6460-6466
   Abstract »    Full Text »    PDF »
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G. R. Tibbs, D. T. Liu, B. G. Leypold, and S. A. Siegelbaum (1998)
J. Biol. Chem. 273, 4497-4505
   Abstract »    Full Text »    PDF »
Dissecting the Cooperative Reassociation of the Regulatory and Catalytic Subunits of cAMP-dependent Protein Kinase. ROLE OF Trp-196 IN THE CATALYTIC SUBUNIT.
R. M. Gibson and S. S. Taylor (1997)
J. Biol. Chem. 272, 31998-32005
   Abstract »    Full Text »    PDF »
Activation by Cyclic GMP Binding Causes an Apparent Conformational Change in cGMP-dependent Protein Kinase.
D.-M. Chu, J. D. Corbin, K. A. Grimes, and S. H. Francis (1997)
J. Biol. Chem. 272, 31922-31928
   Abstract »    Full Text »    PDF »
Progressive Cyclic Nucleotide-induced Conformational Changes in the cGMP-dependent Protein Kinase Studied by Small Angle X-ray Scattering in Solution.
J. Zhao, J. Trewhella, J. Corbin, S. Francis, R. Mitchell, R. Brushia, and D. Walsh (1997)
J. Biol. Chem. 272, 31929-31936
   Abstract »    Full Text »    PDF »
The A-kinase Anchoring Domain of Type IIalpha cAMP-dependent Protein Kinase Is Highly Helical.
M. G. Newlon, M. Roy, Z. E. Hausken, J. D. Scott, and P. A. Jennings (1997)
J. Biol. Chem. 272, 23637-23644
   Abstract »    Full Text »    PDF »
Interaction of the Regulatory and Catalytic Subunits of cAMP-dependent Protein Kinase. ELECTROSTATIC SITES ON THE TYPE Ialpha REGULATORY SUBUNIT.
R. M. Gibson, Y. Ji-Buechler, and S. S. Taylor (1997)
J. Biol. Chem. 272, 16343-16350
   Abstract »    Full Text »    PDF »
Identification of the Amino Acid Sequences Responsible for High Affinity Activation of cGMP Kinase Ialpha.
P. Ruth, A. Pfeifer, S. Kamm, P. Klatt, W. R.G. Dostmann, and F. Hofmann (1997)
J. Biol. Chem. 272, 10522-10528
   Abstract »    Full Text »    PDF »
Mutational Analysis of the A-Kinase Anchoring Protein (AKAP)-binding Site on RII. CLASSIFICATION OF SIDE CHAIN DETERMINANTS FOR ANCHORING AND ISOFORM SELECTIVE ASSOCIATION WITH AKAPs.
Z. E. Hausken, M. L. Dell'Acqua, V. M. Coghlan, and J. D. Scott (1996)
J. Biol. Chem. 271, 29016-29022
   Abstract »    Full Text »    PDF »
Arginine 210Is Not a Critical Residue for the Allosteric Interactions Mediated by Binding of Cyclic AMP to Site A of Regulatory (RIalpha ) Subunit of Cyclic AMP-dependent Protein Kinase.
R. A. Steinberg, M. M. Symcox, S. Sollid, and D. Ogreid (1996)
J. Biol. Chem. 271, 27630-27636
   Abstract »    Full Text »    PDF »
Identification of Key Amino Acids in a Conserved cGMP-binding Site of cGMP-binding Phosphodiesterases. A PUTATIVE NKXnD MOTIF FOR cGMP BINDING.
I. V. Turko, T. L. Haik, L. M. McAllister-Lucas, F. Burns, S. H. Francis, and J. D. Corbin (1996)
J. Biol. Chem. 271, 22240-22244
   Abstract »    Full Text »    PDF »
Fast and Slow Cyclic Nucleotide-dissociation Sites in cAMP-dependent Protein Kinase Are Transposed in Type Ibeta cGMP-dependent Protein Kinase.
R. B. Reed, M. Sandberg, T. Jahnsen, S. M. Lohmann, S. H. Francis, and J. D. Corbin (1996)
J. Biol. Chem. 271, 17570-17575
   Abstract »    Full Text »    PDF »
Mechanism of Regulation of the Epac Family of cAMP-dependent RapGEFs.
J. de Rooij, H. Rehmann, M. van Triest, R. H. Cool, A. Wittinghofer, and J. L. Bos (2000)
J. Biol. Chem. 275, 20829-20836
   Abstract »    Full Text »    PDF »
The Amino-terminal Cyclic Nucleotide Binding Site of the Type II cGMP-dependent Protein Kinase Is Essential for Full Cyclic Nucleotide-dependent Activation.
M. K. Taylor and M. D. Uhler (2000)
J. Biol. Chem. 275, 28053-28062
   Abstract »    Full Text »    PDF »
Differences between Cystic Fibrosis Transmembrane Conductance Regulator and HisP in the Interaction with the Adenine Ring of ATP.
A. L. Berger and M. J. Welsh (2000)
J. Biol. Chem. 275, 29407-29412
   Abstract »    Full Text »    PDF »


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