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Science 26 July 1991: Vol. 253. no. 5018, pp. 407 - 414 DOI: 10.1126/science.1862342
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Articles
Science, Vol 253, Issue 5018, 407-414
Copyright © 1991 by American Association for the Advancement of Science
Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase
DR Knighton,
JH Zheng,
LF Ten Eyck,
VA Ashford,
NH Xuong,
SS Taylor,
and
JM Sowadski
Department of Chemistry, University of California, San Diego, La Jolla 92093-0654.
The crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase complexed with a 20-amino acid substrate analog inhibitor has been solved and partially refined at 2.7 A resolution to an R factor of 0.212. The magnesium adenosine triphosphate (MgATP) binding site was located by difference Fourier synthesis. The enzyme structure is bilobal with a deep cleft between the lobes. The cleft is filled by MgATP and a portion of the inhibitor peptide. The smaller lobe, consisting mostly of amino-terminal sequence, is associated with nucleotide binding, and its largely antiparallel beta sheet architecture constitutes an unusual nucleotide binding motif. The larger lobe is dominated by helical structure with a single beta sheet at the domain interface. This lobe is primarily involved in peptide binding and catalysis. Residues 40 through 280 constitute a conserved catalytic core that is shared by more than 100 protein kinases. Most of the invariant amino acids in this conserved catalytic core are clustered at the sites of nucleotide binding and catalysis.
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- Dual Specificity Protein Kinase Activity of Testis-specific Protein Kinase 1 and Its Regulation by Autophosphorylation of Serine-215 within the Activation Loop.
- J. Toshima, T. Tanaka, and K. Mizuno (1999)
J. Biol. Chem.
274, 12171-12176
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- Phosphatidylinositol Phosphate Kinases, a Multifaceted Family of Signaling Enzymes.
- R. A. Anderson, I. V. Boronenkov, S. D. Doughman, J. Kunz, and J. C. Loijens (1999)
J. Biol. Chem.
274, 9907-9910
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- Inhibition of the Ca2+/Calmodulin-dependent Protein Kinase I Cascade by cAMP-dependent Protein Kinase.
- M. Matsushita and A. C. Nairn (1999)
J. Biol. Chem.
274, 10086-10093
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- Identification of Substrate Binding Site of Cyclin-dependent Kinase 5.
- P. Sharma, P. J. Steinbach, M. Sharma, N. D. Amin, J. J. Barchi Jr., and H. C. Pant (1999)
J. Biol. Chem.
274, 9600-9606
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- Mitogen-Activated Protein Kinases: Specific Messages from Ubiquitous Messengers.
- H. J. Schaeffer and M. J. Weber (1999)
Mol. Cell. Biol.
19, 2435-2444
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- Effects of Phosphorylation of Threonine 160 on Cyclin-dependent Kinase 2 Structure and Activity.
- N. R. Brown, M. E. M. Noble, A. M. Lawrie, M. C. Morris, P. Tunnah, G. Divita, L. N. Johnson, and J. A. Endicott (1999)
J. Biol. Chem.
274, 8746-8756
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- Carboxyl-terminal Phosphorylation Regulates the Function and Subcellular Localization of Protein Kinase C beta II.
- A. S. Edwards, M. C. Faux, J. D. Scott, and A. C. Newton (1999)
J. Biol. Chem.
274, 6461-6468
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- Structural interpretation of site-directed mutagenesis and specificity of the catalytic subunit of protein kinase CK2 using comparative modelling.
- N. Srinivasan, M. Antonelli, G. Jacob, I. Korn, F. Romero, A. Jedlicki, V. Dhanaraj, M. F.-R. Sayed, T. L. Blundell, C. C. Allende, et al. (1999)
Protein Eng. Des. Sel.
12, 119-127
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- Mutation of a highly conserved aspartate residue in subdomain IX abolishes Fer protein-tyrosine kinase activity.
- L.A. Cole, R. Zirngibl, A.W.B. Craig, Z. Jia, and P. Greer (1999)
Protein Eng. Des. Sel.
12, 155-162
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- The CDK-activating Kinase (Cak1p) from Budding Yeast Has an Unusual ATP-binding Pocket.
- D. A. Enke, P. Kaldis, J. K. Holmes, and M. J. Solomon (1999)
J. Biol. Chem.
274, 1949-1956
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- The Caenorhabditis elegans gene ncc-1 encodes a cdc2-related kinase required for M phase in meiotic and mitotic cell divisions, but not for S phase.
- M Boxem, D. Srinivasan, and S van den Heuvel (1999)
Development
126, 2227-2239
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- Deletion of 11 Amino Acids in p90rsk-mo-1 Abolishes Kinase Activity.
- D. J. Spring and E. G. Krebs (1999)
Mol. Cell. Biol.
19, 317-320
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- Mitogen-Activated Protein Kinase: Conservation of a Three-Kinase Module From Yeast to Human.
- C. WIDMANN, S. GIBSON, M. B. JARPE, and G. L. JOHNSON (1999)
Physiol Rev
79, 143-180
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- Binding of 9-Anthroylcholine Monitors the Interactions of Adenosine Cyclic 3',5'-Phosphate-dependent Protein Kinase with MgATP, Substrates, and Regulatory Subunits.
- D. A. Malencik and S. R. Anderson (1998)
J. Biol. Chem.
273, 34049-34056
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- Regulation of Cdc28 Cyclin-Dependent Protein Kinase Activity during the Cell Cycle of the Yeast Saccharomyces cerevisiae.
- M. D. Mendenhall and A. E. Hodge (1998)
Microbiol. Mol. Biol. Rev.
62, 1191-1243
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- Intramolecular Regulatory Interactions in the Src Family Kinase Hck Probed by Mutagenesis of a Conserved Tryptophan Residue.
- M. LaFevre-Bernt, F. Sicheri, A. Pico, M. Porter, J. Kuriyan, and W. T. Miller (1998)
J. Biol. Chem.
273, 32129-32134
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- Quaternary Structures of a Catalytic Subunit-Regulatory Subunit Dimeric Complex and the Holoenzyme of the cAMP-dependent Protein Kinase by Neutron Contrast Variation.
- J. Zhao, E. Hoye, S. Boylan, D. A. Walsh, and J. Trewhella (1998)
J. Biol. Chem.
273, 30448-30459
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- Characterization of Functional Regions in the Schizosaccharomyces pombe mei3 Developmental Activator.
- W. Wang, P. Li, A. Schettino, Z. Peng, and M. McLeod (1998)
Genetics
150, 1007-1018
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- Cleavage and Activation of p21-activated Protein Kinase gamma -PAK by CPP32 (Caspase 3). EFFECTS OF AUTOPHOSPHORYLATION ON ACTIVITY.
- B. N. Walter, Z. Huang, R. Jakobi, P. T. Tuazon, E. S. Alnemri, G. Litwack, and J. A. Traugh (1998)
J. Biol. Chem.
273, 28733-28739
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- Dissecting cAMP Binding Domain A in the RIalpha Subunit of cAMP-dependent Protein Kinase. DISTINCT SUBSITES FOR RECOGNITION OF cAMP AND THE CATALYTIC SUBUNIT.
- L. J.-s. Huang and S. S. Taylor (1998)
J. Biol. Chem.
273, 26739-26746
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