4yff: Difference between revisions
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==TNNI3K complexed with inhibitor 2== | ==TNNI3K complexed with inhibitor 2== | ||
<StructureSection load='4yff' size='340' side='right' caption='[[4yff]], [[Resolution|resolution]] 3.07Å' scene=''> | <StructureSection load='4yff' size='340' side='right' caption='[[4yff]], [[Resolution|resolution]] 3.07Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4yff]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YFF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YFF FirstGlance]. <br> | <table><tr><td colspan='2'>[[4yff]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YFF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YFF FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4CV:3-[(5-BROMO-7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)AMINO]-N-METHYL-4-(MORPHOLIN-4-YL)BENZENESULFONAMIDE'>4CV</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4CV:3-[(5-BROMO-7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)AMINO]-N-METHYL-4-(MORPHOLIN-4-YL)BENZENESULFONAMIDE'>4CV</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4yfi|4yfi]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4yfi|4yfi]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNNI3K, CARK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4yff FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yff OCA], [http://pdbe.org/4yff PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yff RCSB], [http://www.ebi.ac.uk/pdbsum/4yff 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=4yff FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yff OCA], [http://pdbe.org/4yff PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yff RCSB], [http://www.ebi.ac.uk/pdbsum/4yff PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yff ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
[[Category: Lawhorn, B G]] | [[Category: Lawhorn, B G]] | ||
Revision as of 18:22, 16 November 2017
TNNI3K complexed with inhibitor 2TNNI3K complexed with inhibitor 2
Structural highlights
Disease[TNI3K_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. Function[TNI3K_HUMAN] May play a role in cardiac physiology.[1] Publication Abstract from PubMedA series of cardiac troponin I-interacting kinase (TNNI3K) inhibitors arising from 3-((9H-purin-6-yl)amino)-N-methyl-benzenesulfonamide (1) is disclosed along with fundamental structure-function relationships that delineate the role of each element of 1 for TNNI3K recognition. An X-ray structure of 1 bound to TNNI3K confirmed its Type I binding mode and is used to rationalize the structure-activity relationship and employed to design potent, selective, and orally bioavailable TNNI3K inhibitors. Identification of the 7-deazapurine heterocycle as a superior template (vs purine) and its elaboration by introduction of C4-benzenesulfonamide and C7- and C8-7-deazapurine substituents produced compounds with substantial improvements in potency (>1000-fold), general kinase selectivity (10-fold improvement), and pharmacokinetic properties (>10-fold increase in poDNAUC). Optimal members of the series have properties suitable for use in in vitro and in vivo experiments aimed at elucidating the role of TNNI3K in cardiac biology and serve as leads for developing novel heart failure medicines. Identification of Purines and 7-Deazapurines as Potent and Selective Type I Inhibitors of Troponin I-Interacting Kinase (TNNI3K).,Lawhorn BG, Philp J, Zhao Y, Louer C, Hammond M, Cheung M, Fries H, Graves AP, Shewchuk L, Wang L, Cottom JE, Qi H, Zhao H, Totoritis R, Zhang G, Schwartz B, Li H, Sweitzer S, Holt DA, Gatto GJ Jr, Kallander LS J Med Chem. 2015 Sep 24;58(18):7431-48. doi: 10.1021/acs.jmedchem.5b00931. Epub, 2015 Sep 10. PMID:26355916[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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