1LP4

Crystal structure of a binary complex of the catalytic subunit of protein kinase CK2 with Mg-AMPPNP

Summary for 1LP4

• Entry DOI: 10.2210/pdb1lp4/pdb
• Related: 1DAW 1DAY 1JWH 1LPU 1LR4 1QF8
• Descriptor: Protein kinase CK2, MAGNESIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (4 entities in total)
• Functional Keywords: protein kinase, ck2, casein kinase 2, dual-cosubstrate specificity, transferase
• Biological source: Zea mays
• Total number of polymer chains: 1
• Total formula weight: 39845.97

Authors

Niefind, K.,Puetter, M.,Guerra, B.,Issinger, O.-G.,Schomburg, D. (deposition date: 2002-05-07, release date: 2002-05-29, Last modification date: 2024-03-13)

Primary citation

Yde, C.W.,Ermakova, I.,Issinger, O.G.,Niefind, K.
Inclining the purine base binding plane in protein kinase CK2 by exchanging the flanking side-chains generates a preference for ATP as a cosubstrate.
J.Mol.Biol., 347:399-414, 2005

PubMed Abstract: Protein kinase CK2 (casein kinase 2) is a highly conserved and ubiquitously found eukaryotic serine/threonine kinase that plays a role in various cellular key processes like proliferation, apoptosis and circadian rhythm. One of its prominent biochemical properties is its ability to use GTP as well as ATP as a cosubstrate (dual-cosubstrate specificity). This feature is exceptional among eukaryotic protein kinases, and its biological significance is unknown. We describe here a mutant of the catalytic subunit of protein kinase CK2 (CK2alpha) from Homo sapiens (hsCK2alpha) with a clear and CK2-atypical preference for ATP compared to GTP. This mutant was designed on the basis of several structures of CK2alpha from Zea mays (zmCK2alpha) in complex with various ATP-competitive ligands. A structural overlay revealed the existence of a "purine base binding plane" harbouring the planar moiety of the respective ligand like the purine base of ATP and GTP. This purine base binding plane is sandwiched between the side-chains of Ile66 (Val66 in hsCK2alpha) and Met163, and it adopts a significantly different orientation than in prominent homologues like cAMP-dependent protein kinase (CAPK). By exchanging these two flanking amino acids (Val66Ala, Met163Leu) in hsCK2alpha(1-335), a C-terminally truncated variant of hsCK2alpha, the cosubstrate specificity shifted in the expected direction so that the mutant strongly favours ATP. A structure determination of the mutant in complex with an ATP-analogue confirmed the predicted change of the purine base binding plane orientation. An unexpected but in retrospect plausible consequence of the mutagenesis was, that the helix alpha D region, which is in the direct neighbourhood of the ATP-binding site, has adopted a conformation that is more similar to CAPK and less favourable for binding of GTP. These findings demonstrate that CK2alpha possesses sophisticated structural adaptations in favour of dual-cosubstrate specificity, suggesting that this property could be of biological significance.

PubMed: 15740749
DOI: 10.1016/j.jmb.2005.01.003

Experimental method

X-RAY DIFFRACTION (1.86 Å)