Proteopedia

6isj: Difference between revisions

← Older edit
No edit summary
No edit summary
 
Line 3: Line 3:
<StructureSection load='6isj' size='340' side='right'caption='[[6isj]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
<StructureSection load='6isj' size='340' side='right'caption='[[6isj]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6isj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ISJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ISJ FirstGlance]. <br>
<table><tr><td colspan='2'>[[6isj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryptococcus_neoformans_var._grubii_Bt85 Cryptococcus neoformans var. grubii Bt85]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ISJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ISJ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3NG:5-[(3-CHLOROPHENYL)AMINO]BENZO[C][2,6]NAPHTHYRIDINE-8-CARBOXYLIC+ACID'>3NG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</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=6isj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6isj OCA], [http://pdbe.org/6isj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6isj RCSB], [http://www.ebi.ac.uk/pdbsum/6isj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6isj ProSAT]</span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3NG:5-[(3-CHLOROPHENYL)AMINO]BENZO[C][2,6]NAPHTHYRIDINE-8-CARBOXYLIC+ACID'>3NG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6isj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6isj OCA], [https://pdbe.org/6isj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6isj RCSB], [https://www.ebi.ac.uk/pdbsum/6isj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6isj ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
5-(3-chlorophenylamino)benzo[c][2,6] naphthyridine-8 carboxylic acid (CX-4945), the first clinical stage inhibitor of protein kinase CK2 for the treatment of cancer, is representative of a new class of CK2 inhibitors with Ki values in the low nanomolar range and unprecedented selectivity versus other kinases. Here we present the crystal structure of the complexes between CX-4945 and two analogs (CX-5011 and CX-5279) with the catalytic subunit of human CK2. Consistent with their ATP competitive mode of inhibition, all three compounds bind in the active site of CK2 (Type I inhibitors). The tricyclic scaffold of the inhibitors superposes to the adenine of ATP establishing multiple hydrophobic interactions with the binding cavity. The more extended scaffold, as compared to that of ATP, allows the carboxylic function, shared by all three ligands, to penetrate into the deepest part of the active site where it makes interactions with conserved water W1 and Lys-68, thus accounting for the crucial role of this negatively charged group in conferring high potency to this class of inhibitors. The presence of a pyrimidine in CX-5011 and in CX-5279 instead of a pyridine (as in CX-4945) ring is likely to account for the higher specificity of these compounds whose Gini coefficients, calculated by profiling them against panels of 102 and/or 235 kinases, are significantly higher than that of CX-4945 (0.735 and 0.755 respectively, vs 0.615), denoting the highest selectivity ever reported for CK2 inhibitors.


Unprecedented selectivity and structural determinants of a new class of protein kinase CK2 inhibitors in clinical stage for the treatment of cancer.,Battistutta R, Cozza G, Pierre F, Papinutto E, Lolli G, Sarno S, O'Brien SE, Siddiqui-Jain A, Haddach M, Anderes K, Ryckman DM, Meggio F, Pinna LA Biochemistry. 2011 Aug 26. PMID:21870818<ref>PMID:21870818</ref>
==See Also==
 
*[[Casein kinase 3D structures|Casein kinase 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6isj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Cryptococcus neoformans var. grubii Bt85]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Cho, H S]]
[[Category: Cho HS]]
[[Category: Kinase]]
[[Category: Transferase]]

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/w/6isj"