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| - | [[Image:3bw5.jpg|left|200px]]<br /><applet load="3bw5" size="350" color="white" frame="true" align="right" spinBox="true" | + | #REDIRECT [[3juh]] This PDB entry is obsolete and replaced by 3juh |
| - | caption="3bw5, resolution 1.66Å" />
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| - | '''Crystal structure of a mutant of human protein kinase CK2alpha with altered cosubstrate specificity'''<br />
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| - | ==Overview==
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| - | 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.
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| - | ==About this Structure==
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| - | 3BW5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=ANP:'>ANP</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 1YMI. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BW5 OCA].
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| - | ==Reference==
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| - | Inclining the purine base binding plane in protein kinase CK2 by exchanging the flanking side-chains generates a preference for ATP as a cosubstrate., Yde CW, Ermakova I, Issinger OG, Niefind K, J Mol Biol. 2005 Mar 25;347(2):399-414. Epub 2005 Jan 18. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15740749 15740749]
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| - | [[Category: Homo sapiens]]
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| - | [[Category: Non-specific serine/threonine protein kinase]]
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| - | [[Category: Single protein]]
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| - | [[Category: Ermakova, I.]]
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| - | [[Category: Issinger, O G.]]
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| - | [[Category: Niefind, K.]]
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| - | [[Category: Raaf, J.]]
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| - | [[Category: Yde, C W.]]
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| - | [[Category: ANP]]
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| - | [[Category: CL]]
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| - | [[Category: GOL]]
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| - | [[Category: atp-binding]]
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| - | [[Category: casein kinase 2]]
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| - | [[Category: casein kinase ii]]
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| - | [[Category: nucleotide-binding]]
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| - | [[Category: protein kinase ck2]]
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| - | [[Category: serine/threonine-protein kinase]]
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| - | [[Category: transferase]]
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| - | [[Category: wnt signaling pathway]]
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| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:07:45 2008''
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