1FOT

Structure of the unliganded cAMP-dependent protein kinase catalytic subunit from Saccharomyces cerevisiae.

(2001) Arch Biochem Biophys 387: 11-19

• PubMed: 11368172 Search on PubMed
• DOI: https://doi.org/10.1006/abbi.2000.2241
• Primary Citation of Related Structures:  
  1FOT


• PubMed Abstract: 
  

  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.

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Organizational Affiliation: 

Biophysics Program, Ohio State University Medical School, Columbus 43210, USA.