3u87

Publication Abstract from PubMed

A low-resolution structure of the catalytic subunit CK2alpha of human protein kinase CK2 (formerly known as casein kinase 2) in complex with the ATP-competitive inhibitor resorufin is presented. The structure supplements previous human CK2alpha structures in which the interdomain hinge/helix alphaD region adopts a closed conformation correlating to a canonically established catalytic spine as is typical for eukaryotic protein kinases. In the corresponding crystal packing the hinge/helix alphaD region is nearly unaffected by crystal contacts, so that largely unbiased conformational adaptions are possible. This is documented by published human CK2alpha structures with the same crystal packing but with an open hinge/helix alphaD region, one of which has been redetermined here with a higher symmetry. An overview of all published human CK2alpha crystal packings serves as the basis for a discussion of the factors that determine whether the open or the closed hinge/helix alphaD conformation is adopted. Lyotropic salts in crystallization support the closed conformation, in which the Phe121 side chain complements the hydrophobic catalytic spine ensemble. Consequently, genuine ligand effects on the hinge/helix alphaD conformation can be best studied under moderate salt conditions. Ligands that stabilize either the open or the closed conformation by hydrogen bonds are known, but a general rule is not yet apparent.

Low-density crystal packing of human protein kinase CK2 catalytic subunit in complex with resorufin or other ligands: a tool to study the unique hinge-region plasticity of the enzyme without packing bias.,Klopffleisch K, Issinger OG, Niefind K Acta Crystallogr D Biol Crystallogr. 2012 Aug;68(Pt 8):883-92. Epub 2012 Jul 7. PMID:22868753^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.