1m2q: Difference between revisions
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[[Image: | ==Crystal structure of 1,8-di-hydroxy-4-nitro-xanten-9-one/CK2 kinase complex== | ||
<StructureSection load='1m2q' size='340' side='right' caption='[[1m2q]], [[Resolution|resolution]] 1.79Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1m2q]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Zea_mays Zea mays]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M2Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1M2Q FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MNX:1,8-DI-HYDROXY-4-NITRO-XANTHEN-9-ONE'>MNX</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1j91|1j91]], [[1jam|1jam]], [[1f0q|1f0q]], [[1m2p|1m2p]]</td></tr> | |||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1m2q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m2q OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1m2q RCSB], [http://www.ebi.ac.uk/pdbsum/1m2q PDBsum]</span></td></tr> | |||
<table> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/m2/1m2q_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Protein kinases play key roles in signal transduction and therefore are among the most attractive targets for drug design. The pharmacological aptitude of protein kinase inhibitors is highlighted by the observation that various diseases with special reference to cancer are because of the abnormal expression/activity of individual kinases. The resolution of the three-dimensional structure of the target kinase in complex with inhibitors is often the starting point for the rational design of this kind of drugs, some of which are already in advanced clinical trial or even in clinical practice. Here we present and discuss three new crystal structures of ATP site-directed inhibitors in complex with "casein kinase-2" (CK2), a constitutively active protein kinase implicated in a variety of cellular functions and misfunctions. With the help of theoretical calculations, we disclose some key features underlying the inhibitory efficiency of anthraquinone derivatives, outlining three different binding modes into the active site. In particular, we show that a nitro group in a hydroxyanthraquinone scaffold decreases the inhibitory constants K(i) because of electron-withdrawing and resonance effects that enhance the polarization of hydroxylic substituents in paraposition. | |||
Inhibition of protein kinase CK2 by anthraquinone-related compounds. A structural insight.,De Moliner E, Moro S, Sarno S, Zagotto G, Zanotti G, Pinna LA, Battistutta R J Biol Chem. 2003 Jan 17;278(3):1831-6. Epub 2002 Nov 4. PMID:12419810<ref>PMID:12419810</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Casein kinase|Casein kinase]] | *[[Casein kinase|Casein kinase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
[[Category: Zea mays]] | [[Category: Zea mays]] | ||
Revision as of 16:41, 28 September 2014
Crystal structure of 1,8-di-hydroxy-4-nitro-xanten-9-one/CK2 kinase complexCrystal structure of 1,8-di-hydroxy-4-nitro-xanten-9-one/CK2 kinase complex
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedProtein kinases play key roles in signal transduction and therefore are among the most attractive targets for drug design. The pharmacological aptitude of protein kinase inhibitors is highlighted by the observation that various diseases with special reference to cancer are because of the abnormal expression/activity of individual kinases. The resolution of the three-dimensional structure of the target kinase in complex with inhibitors is often the starting point for the rational design of this kind of drugs, some of which are already in advanced clinical trial or even in clinical practice. Here we present and discuss three new crystal structures of ATP site-directed inhibitors in complex with "casein kinase-2" (CK2), a constitutively active protein kinase implicated in a variety of cellular functions and misfunctions. With the help of theoretical calculations, we disclose some key features underlying the inhibitory efficiency of anthraquinone derivatives, outlining three different binding modes into the active site. In particular, we show that a nitro group in a hydroxyanthraquinone scaffold decreases the inhibitory constants K(i) because of electron-withdrawing and resonance effects that enhance the polarization of hydroxylic substituents in paraposition. Inhibition of protein kinase CK2 by anthraquinone-related compounds. A structural insight.,De Moliner E, Moro S, Sarno S, Zagotto G, Zanotti G, Pinna LA, Battistutta R J Biol Chem. 2003 Jan 17;278(3):1831-6. Epub 2002 Nov 4. PMID:12419810[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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