cAMP-dependent protein kinase defines a family of enzymes
| Autor: | Friedrich W. Herberg, W. M. Yonemoto, Jianhua Zheng, L. F. Ten Eyck, E. Radzio-Andzelm, Susan S. Taylor, D. R. Knighton, J. M. Sowadski |
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| Rok vydání: | 1993 |
| Předmět: |
Models
Molecular Consensus site Sequence Homology Amino Acid Macromolecular Substances Protein subunit Molecular Sequence Data Biology General Biochemistry Genetics and Molecular Biology Protein Structure Secondary Mice Protein structure Biochemistry Phosphoprotein Multigene Family Cyclin-dependent kinase complex Animals Amino Acid Sequence General Agricultural and Biological Sciences Protein kinase A Peptide sequence Ternary complex Protein Kinases |
| Zdroj: | Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 340(1293) |
| ISSN: | 0962-8436 |
| Popis: | The structure of the recombinant mouse catalytic subunit of cAMP-dependent protein kinase is reviewed with particular emphasis on the overall features and specific amino acids that are shared by all members of the eukaryotic protein kinase family. The crystal structure of a ternary complex containing both MgATP and a twenty-residue inhibitor peptide defines the precise role of the conserved residues that are clustered at the active site. In addition to catalysing the post-translational modification of other proteins, the catalytic subunit is itself subject to covalent modifications. It is a phosphoprotein and is also myristylated at its amino terminus. The enzyme when crystallized in the presence of detergent shows a detergent molecule bound to an acyl pocket that is presumably occupied by the myristyl moiety in the mammalian enzyme. When expressed in E.coli , the catalytic subunit is autophosphorylated at four sites. Two stable phosphates at Ser338 and Thrl97 interact with multiple protein side chains thus explaining why they are inaccessible to phosphatases. Although all substrates and inhibitors of the catalytic subunit share a general minimum consensus sequence, the high affinity binding of protein inhibitors such as the regulatory subunits and the heat stable protein kinase inhibitors require additional determinants that lie beyond the consensus site. These two physiological inhibitors of the catalytic subunit appear to use different sites to achieve high-affinity binding. |
| Databáze: | OpenAIRE |
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