Structure of the Unliganded cAMP-Dependent Protein Kinase Catalytic Subunit from Saccharomyces cerevisiae
| Autor: | Jeff Kuret, Neda Mashhoon, Gilles Carmel, James W. Pflugrath |
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| Rok vydání: | 2001 |
| Předmět: |
Models
Molecular Protein Conformation Protein subunit Molecular Sequence Data Saccharomyces cerevisiae Biophysics Crystallography X-Ray Ligands Biochemistry Catalysis Substrate Specificity Evolution Molecular Protein structure Species Specificity Catalytic Domain Transferase Nucleotide Amino Acid Sequence Protein kinase A Molecular Biology Sequence Deletion chemistry.chemical_classification Sequence Homology Amino Acid biology Active site biology.organism_classification Cyclic AMP-Dependent Protein Kinases Peptide Fragments Protein Subunits Crystallography chemistry Mutation biology.protein Cyclin-dependent kinase complex |
| Zdroj: | Archives of Biochemistry and Biophysics. 387:11-19 |
| ISSN: | 0003-9861 |
| DOI: | 10.1006/abbi.2000.2241 |
| Popis: | The structure of TPK1delta, a truncated variant of the cAMP-dependent protein kinase catalytic subunit from Saccharomyces cerevisiae, was determined in an unliganded state at 2.8 A resolution and refined to a crystallographic R-factor of 19.4%. Comparison of this structure to that of its fully liganded mammalian homolog revealed a highly conserved protein fold comprised of two globular lobes. Within each lobe, root mean square deviations in Calpha positions averaged approximately equals 0.9 A. In addition, a phosphothreonine residue was found in the C-terminal domain of each enzyme. Further comparison of the two structures suggests that a trio of conformational changes accompanies ligand-binding. The first consists of a 14.7 degrees rigid-body rotation of one lobe relative to the other and results in closure of the active site cleft. The second affects only the glycine-rich nucleotide binding loop, which moves approximately equals 3 A to further close the active site and traps the nucleotide substrate. The third is localized to a C-terminal segment that makes direct contact with ligands and the ligand-binding cleft. In addition to resolving the conformation of unliganded enzyme, the model shows that the salient features of the cAMP-dependent protein kinase are conserved over long evolutionary distances. |
| Databáze: | OpenAIRE |
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