Open and Closed Conformations of the cAMP dependent Protein Kinase Catalytic Subunit

The figure above illustrates the open and closed conformations of the catalytic subunit of cAMP depdendant protein kinase. Purple is 1ATP in a closed conformation and yellow is 1CMK in an open conformation. A full description of the similarities and differences in these two conformations is given in Protein Sci 2: 1559-73 (1993). A brief synopsis is given here.

Most movement is in the small nucleotide binding lobe, which appears to twist in a clockwise direction upon ATP binding. The major changes are in the C terminal 30 residues shown at the top of the figure and in the interaction of the glycine rich loop with the phosphoryaltion site Thr197.

This movement is distinctive within the known kinase structures - that is all structures cluster around one of the two distinct conformations as indicated by the following:

red open / black closed

RMS A / Sequence Homology %

1CMK:E 1ATP:E 1CDK:A 1CDK:B 1APM:E 1CTP:E 2CPK:E PK06
1CMK:E 0.0
1ATP:E 1.82/97.1 0.0
1CDK:A 1.97/100 0.36/97.1 0.0
1CDK:B 1.90/100 0.34/97.1 0.29/100 0.0
1APM:E 1.81/96.9 0.32/99.7 0.37/96.9 0.34/99.7 0.0
1CTP:E 0.73/99.7 1.75/97.4 1.88/99.7 1.82/97.4 1.72/97.1 0.0
2CPK:E 1.69/97.1 0.37/100 0.44/97.1 0.38/97.1 0.30/99.7 1.67/97.4 0.0
PK06 1.74/88.0 0.35/90.9 0.43/88.0 0.39/88.0 0.23/ 90.9 1.67/88.3 0.36/90.9 0.0

Two numbers are given for each structure/sequence superposition. The RMS is determined by sequence alignment followed by structure superposition of those residues found to align in the sequence. Structure superposition uses minimization of the Calpha positions by the method of least-squares. Sequence homology is reported as a percentage.