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==TNNI3K complexed with a 4,6-diaminopyrimidine==
==TNNI3K complexed with a 4,6-diaminopyrimidine==
<StructureSection load='6b5j' size='340' side='right' caption='[[6b5j]], [[Resolution|resolution]] 2.97&Aring;' scene=''>
<StructureSection load='6b5j' size='340' side='right'caption='[[6b5j]], [[Resolution|resolution]] 2.97&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6b5j]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B5J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B5J FirstGlance]. <br>
<table><tr><td colspan='2'>[[6b5j]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B5J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B5J FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CV4:N-methyl-3-[(6-{[4-(trifluoromethyl)phenyl]amino}pyrimidin-4-yl)amino]benzene-1-sulfonamide'>CV4</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]] 2.97&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CV4:N-methyl-3-[(6-{[4-(trifluoromethyl)phenyl]amino}pyrimidin-4-yl)amino]benzene-1-sulfonamide'>CV4</scene></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=6b5j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b5j OCA], [http://pdbe.org/6b5j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b5j RCSB], [http://www.ebi.ac.uk/pdbsum/6b5j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b5j ProSAT]</span></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=6b5j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b5j OCA], [https://pdbe.org/6b5j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b5j RCSB], [https://www.ebi.ac.uk/pdbsum/6b5j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b5j ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/TNI3K_HUMAN TNI3K_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry.  
[https://www.uniprot.org/uniprot/TNI3K_HUMAN TNI3K_HUMAN] The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/TNI3K_HUMAN TNI3K_HUMAN]] May play a role in cardiac physiology.<ref>PMID:12721663</ref>
[https://www.uniprot.org/uniprot/TNI3K_HUMAN TNI3K_HUMAN] May play a role in cardiac physiology.<ref>PMID:12721663</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Structure-guided progression of a purine-derived series of TNNI3K inhibitors directed design efforts that produced a novel series of 4,6-diaminopyrimidine inhibitors, an emerging kinase binding motif. Herein, we report a detailed understanding of the intrinsic conformational preferences of the scaffold, which impart high specificity for TNNI3K. Further manipulation of the template based on the conformational analysis and additional structure-activity relationship studies provided enhancements in kinase selectivity and pharmacokinetics that furnished an advanced series of potent inhibitors. The optimized compounds (e.g., GSK854) are suitable leads for identifying new cardiac medicines and have been employed as in vivo tools in investigational studies aimed at defining the role of TNNI3K within heart failure.


4,6-Diaminopyrimidines as Highly Preferred Troponin I-Interacting Kinase (TNNI3K) Inhibitors.,Philp J, Lawhorn BG, Graves AP, Shewchuk L, Rivera KL, Jolivette LJ, Holt DA, Gatto GJ Jr., Kallander LS J Med Chem. 2018 Mar 21. doi: 10.1021/acs.jmedchem.8b00125. PMID:29561151<ref>PMID:29561151</ref>
==See Also==
 
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6b5j" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Homo sapiens]]
[[Category: Philp, J]]
[[Category: Large Structures]]
[[Category: Shewchuk, L M]]
[[Category: Philp J]]
[[Category: Kinase]]
[[Category: Shewchuk LM]]
[[Category: Transferase-transferase inhibitor complex]]

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