The structure of two kinases from crystalographic data.

Overview of the structure of cAMP-dependent protein kinase (PKA).

Additional analyses of PKA structure/function are linked here.

( Viewing the files at the above link requires installation of the helper application "Mage" into your web browser. )

Overview of the structure of cyclin-dependent protein kinase 2 (cdk2).

The structure of calmodulin-dependent kinase II.

Overlay of the CamKII regulatory sites on PKA.

Overlay of the CamKII regulatory sites on cdk2.

Conclusion: comparison of these overlays suggests that the CaMKII autoinhibitory domain, which must be able to occupy the peptide substrate site, must more closely conform to the topology of the analog site of PKA rather than that of cdk2.

Published models of CaMKII are discussed here

and here.

The calmodulin-binding site of CaMKII is an alpha helix composed of residues 293-310. The structure of crystals of calmodulin complexed with the CaMKII binding-site peptide have been obtained.

Here are two views of calmodulin complexed with the 293-310 CaMKII peptide.

And views of the CaMKII calmodulin-binding residues (293-310) in the conformation that occurs when they are bound to calmodulin.

Finally... a composite model of calmodulin bound to the analog site on PKA that may resemble the CaMKII subunit/complex with calmodulin .

e-mail: rwalbers@helix.nih.gov