A Critical Look at the Crystal Structures of cAMP-Dependent Protein Kinases

Area of Science:

• Structural Biology
• Biochemistry

Background:

• The Protein Data Bank (PDB) contains numerous structural deposits for cAMP-dependent protein kinases (PKA).
• Assessing the quality of these structures is crucial for understanding PKA function and for guiding future research.

Purpose of the Study:

• To evaluate the quality of PKA catalytic domain crystal structures in the PDB.
• To assess the effectiveness of the PDB-REDO pipeline in improving structural models.

Main Methods:

• Analysis of 289 PDB crystal structure deposits with atomic coordinates and structure factors.
• Comparison of structure quality indicators before and after re-refinement using PDB-REDO.
• Detailed examination of small-molecule ligand quality within the structures.

Main Results:

• Most PDB deposits for PKA catalytic domains were of acceptable quality, with newer structures generally superior to older ones.
• The PDB-REDO re-refinement procedure showed significant improvement primarily in older structures; its overall impact was limited.
• Small-molecule ligands within the evaluated structures generally exhibited good fit to the electron density.

Conclusions:

• While minor issues were noted, PKA crystal structures in the PDB are largely of good quality.
• Automated re-refinement offers benefits mainly for older structural models, with limited impact on recent, high-quality structures.
• This quality assessment methodology can be extended to other protein families to identify high-resolution structural data.