3bqc
From Proteopedia
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| - | [[Image:3bqc.jpg|left|200px]] | + | [[Image:3bqc.jpg|left|200px]] |
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| - | '''High pH-value crystal structure of emodin in complex with the catalytic subunit of protein kinase CK2''' | + | {{Structure |
| + | |PDB= 3bqc |SIZE=350|CAPTION= <scene name='initialview01'>3bqc</scene>, resolution 1.50Å | ||
| + | |SITE= <scene name='pdbsite=AC1:Cl+Binding+Site+For+Residue+A+336'>AC1</scene>, <scene name='pdbsite=AC2:Cl+Binding+Site+For+Residue+A+337'>AC2</scene> and <scene name='pdbsite=AC3:Emo+Binding+Site+For+Residue+A+400'>AC3</scene> | ||
| + | |LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene> and <scene name='pdbligand=EMO:3-METHYL-1,6,8-TRIHYDROXYANTHRAQUINONE'>EMO</scene> | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= csnk2a1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''High pH-value crystal structure of emodin in complex with the catalytic subunit of protein kinase CK2''' | ||
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| + | ==Overview== | ||
| + | The Ser/Thr kinase CK2 (former name: casein kinase 2) is a heterotetrameric enzyme composed of two catalytic chains (CK2alpha) attached to a dimer of noncatalytic subunits. Together with the cyclin-dependent kinases and the mitogen-activated protein kinases, CK2alpha belongs to the CMGC family of the eukaryotic protein kinases. CK2 is an important survival and stability factor in eukaryotic cells: its catalytic activity is elevated in a wide variety of tumors while its down-regulation can lead to apoptosis. Thus, CK2 is a valuable target for drug development and for chemical biology approaches of cell biological research, and small organic inhibitors addressing CK2 are of considerable interest. We describe here the complex structure between a C-terminal deletion mutant of human CK2alpha and the ATP-competitive inhibitor emodin (1,3,8-trihydroxy-6-methylanthraquinone, International Union of Pure and Applied Chemistry name: 1,3,8-trihydroxy-6-methylanthracene-9,10-dione) and compare it with a previously published complex structure of emodin and maize CK2alpha. With a resolution of 1.5 A, the human CK2alpha/emodin structure has a much better resolution than its maize counterpart (2.6 A). Even more important, in spite of a sequence identity of more than 77% between human and maize CK2alpha, the two structures deviate significantly in the orientation, in which emodin is trapped by the enzyme, and in the local conformations around the ligand binding site: maize CK2alpha shows its largest adaptations in the ATP-binding loop, whereas human CK2alpha shows its largest adaptations in the hinge region connecting the two main domains of the protein kinase core. These observations emphasize the importance of local plasticity for ligand binding and demonstrate that two orthologues of an enzyme can behave quite different in this respect. | ||
==About this Structure== | ==About this Structure== | ||
| - | 3BQC is a [ | + | 3BQC is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BQC OCA]. |
| + | |||
| + | ==Reference== | ||
| + | The catalytic subunit of human protein kinase CK2 structurally deviates from its maize homologue in complex with the nucleotide competitive inhibitor emodin., Raaf J, Klopffleisch K, Issinger OG, Niefind K, J Mol Biol. 2008 Mar 14;377(1):1-8. Epub 2008 Jan 11. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18242640 18242640] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
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[[Category: casein kinase 2]] | [[Category: casein kinase 2]] | ||
[[Category: emodin]] | [[Category: emodin]] | ||
| - | [[Category: eukaryotic protein | + | [[Category: eukaryotic protein kinase]] |
[[Category: nucleotide-binding]] | [[Category: nucleotide-binding]] | ||
[[Category: protein kinase ck2]] | [[Category: protein kinase ck2]] | ||
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[[Category: wnt signaling pathway]] | [[Category: wnt signaling pathway]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 19:00:38 2008'' |
Revision as of 17:00, 20 March 2008
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| , resolution 1.50Å | |||||||
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| Sites: | , and | ||||||
| Ligands: | and | ||||||
| Gene: | csnk2a1 (Homo sapiens) | ||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
High pH-value crystal structure of emodin in complex with the catalytic subunit of protein kinase CK2
Overview
The Ser/Thr kinase CK2 (former name: casein kinase 2) is a heterotetrameric enzyme composed of two catalytic chains (CK2alpha) attached to a dimer of noncatalytic subunits. Together with the cyclin-dependent kinases and the mitogen-activated protein kinases, CK2alpha belongs to the CMGC family of the eukaryotic protein kinases. CK2 is an important survival and stability factor in eukaryotic cells: its catalytic activity is elevated in a wide variety of tumors while its down-regulation can lead to apoptosis. Thus, CK2 is a valuable target for drug development and for chemical biology approaches of cell biological research, and small organic inhibitors addressing CK2 are of considerable interest. We describe here the complex structure between a C-terminal deletion mutant of human CK2alpha and the ATP-competitive inhibitor emodin (1,3,8-trihydroxy-6-methylanthraquinone, International Union of Pure and Applied Chemistry name: 1,3,8-trihydroxy-6-methylanthracene-9,10-dione) and compare it with a previously published complex structure of emodin and maize CK2alpha. With a resolution of 1.5 A, the human CK2alpha/emodin structure has a much better resolution than its maize counterpart (2.6 A). Even more important, in spite of a sequence identity of more than 77% between human and maize CK2alpha, the two structures deviate significantly in the orientation, in which emodin is trapped by the enzyme, and in the local conformations around the ligand binding site: maize CK2alpha shows its largest adaptations in the ATP-binding loop, whereas human CK2alpha shows its largest adaptations in the hinge region connecting the two main domains of the protein kinase core. These observations emphasize the importance of local plasticity for ligand binding and demonstrate that two orthologues of an enzyme can behave quite different in this respect.
About this Structure
3BQC is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The catalytic subunit of human protein kinase CK2 structurally deviates from its maize homologue in complex with the nucleotide competitive inhibitor emodin., Raaf J, Klopffleisch K, Issinger OG, Niefind K, J Mol Biol. 2008 Mar 14;377(1):1-8. Epub 2008 Jan 11. PMID:18242640
Page seeded by OCA on Thu Mar 20 19:00:38 2008
Categories: Homo sapiens | Non-specific serine/threonine protein kinase | Single protein | Issinger, O G. | Niefind, K. | Raaf, J. | CL | EMO | Atp-binding | Atp-competitive inhibitor | Casein kinase 2 | Emodin | Eukaryotic protein kinase | Nucleotide-binding | Protein kinase ck2 | Serine/threonine-protein kinase | Transferase | Wnt signaling pathway
