3pwd: Difference between revisions
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==Crystal structure of maize CK2 in complex with NBC (Z1)== | ==Crystal structure of maize CK2 in complex with NBC (Z1)== | ||
<StructureSection load='3pwd' size='340' side='right' caption='[[3pwd]], [[Resolution|resolution]] 2.20Å' scene=''> | <StructureSection load='3pwd' size='340' side='right' caption='[[3pwd]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3pwd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3pwd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Maize Maize]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PWD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PWD FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CZ0:8-HYDROXY-4-METHYL-9-NITRO-2H-BENZO[G]CHROMEN-2-ONE'>CZ0</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CZ0:8-HYDROXY-4-METHYL-9-NITRO-2H-BENZO[G]CHROMEN-2-ONE'>CZ0</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4577 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4577 MAIZE])</td></tr> | ||
<tr id='activity'><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 id='activity'><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 id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3pwd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pwd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3pwd RCSB], [http://www.ebi.ac.uk/pdbsum/3pwd PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3pwd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pwd OCA], [http://pdbe.org/3pwd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3pwd RCSB], [http://www.ebi.ac.uk/pdbsum/3pwd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3pwd ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3pwd" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Maize]] | |||
[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
[[Category: Battistutta, R]] | [[Category: Battistutta, R]] | ||
[[Category: Mazzorana, M]] | [[Category: Mazzorana, M]] | ||
Revision as of 05:11, 5 August 2016
Crystal structure of maize CK2 in complex with NBC (Z1)Crystal structure of maize CK2 in complex with NBC (Z1)
Structural highlights
Function[CSK2A_MAIZE] Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. The alpha chain contains the catalytic site. Publication Abstract from PubMed8-hydroxy-4-methyl-9-nitrobenzo(g)chromen-2-one (NBC) has been found to be a fairly potent ATP site-directed inhibitor of protein kinase CK2 (Ki = 0.22 muM). Here, we show that NBC also inhibits PIM kinases, especially PIM1 and PIM3, the latter as potently as CK2. Upon removal of the nitro group, to give 8-hydroxy-4-methyl-benzo(g)chromen-2-one (here referred to as "denitro NBC", dNBC), the inhibitory power toward CK2 is almost entirely lost (IC(50) > 30 muM) whereas that toward PIM1 and PIM3 is maintained; in addition, dNBC is a potent inhibitor of a number of other kinases that are weakly inhibited or unaffected by NBC, with special reference to DYRK1A whose IC(50) values with NBC and dNBC are 15 and 0.60 muM, respectively. Therefore, the observation that NBC, unlike dNBC, is a potent inducer of apoptosis is consistent with the notion that this effect is mediated by inhibition of endogenous CK2. The structural features underlying NBC selectivity have been revealed by inspecting its 3D structure in complex with the catalytic subunit of Z. mays CK2. The crucial role of the nitro group is exerted both through a direct electrostatic interaction with the side chain of Lys68 and, indirectly, by enhancing the acidic dissociation constant of the adjacent hydroxyl group which interacts with a conserved water molecule in the deepest part of the cavity. By contrast, the very same nitro group is deleterious for the binding to the active site of DYRK1A, as disclosed by molecular docking. This provides the rationale for preferential inhibition of DYRK1A by dNBC. Structural features underlying the selectivity of the kinase inhibitors NBC and dNBC: role of a nitro group that discriminates between CK2 and DYRK1A.,Sarno S, Mazzorana M, Traynor R, Ruzzene M, Cozza G, Pagano MA, Meggio F, Zagotto G, Battistutta R, Pinna LA Cell Mol Life Sci. 2011 Jul 1. PMID:21720886[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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