5t8o

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'''Unreleased structure'''
 
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The entry 5t8o is ON HOLD until Paper Publication
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==Crystal structure of murine NF-kappaB inducing kinase (NIK) bound to Imidazobenzoxepin Compound 3==
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<StructureSection load='5t8o' size='340' side='right' caption='[[5t8o]], [[Resolution|resolution]] 2.41&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[5t8o]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T8O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T8O FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=76Z:10-(3-METHYL-3-OXIDANYL-BUT-1-YNYL)-5,6-DIHYDROIMIDAZO[1,2-D][1,4]BENZOXAZEPINE-2-CARBOXAMIDE'>76Z</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </span></td></tr>
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<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=5t8o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t8o OCA], [http://pdbe.org/5t8o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t8o RCSB], [http://www.ebi.ac.uk/pdbsum/5t8o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t8o ProSAT]</span></td></tr>
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</table>
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== Function ==
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[[http://www.uniprot.org/uniprot/M3K14_MOUSE M3K14_MOUSE]] Lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity. Promotes proteolytic processing of NFKB2/P100, which leads to activation of NF-kappa-B via the non-canonical pathway. Could act in a receptor-selective manner.<ref>PMID:11239468</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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We report here structure-guided optimization of a novel series of NF-kappaB inducing kinase (NIK) inhibitors. Starting from a modestly potent, low molecular weight lead, activity was improved by designing a type 11/2 binding mode that accessed a back pocket past the methionine-471 gatekeeper. Divergent binding modes in NIK and PI3K were exploited to dampen PI3K inhibition while maintaining NIK inhibition within these series. Potent compounds were discovered that selectively inhibit the nuclear translocation of NF-kappaB2 (p52/REL-B) but not canonical NF-kappaB1 (REL-A/p50).
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Authors:
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Structure-Based Design of Tricyclic NF-kappaB Inducing Kinase (NIK) Inhibitors That Have High Selectivity over Phosphoinositide-3-kinase (PI3K).,Castanedo GM, Blaquiere N, Beresini M, Bravo B, Brightbill H, Chen J, Cui HF, Eigenbrot C, Everett C, Feng J, Godemann R, Gogol E, Hymowitz S, Johnson A, Kayagaki N, Kohli PB, Knuppel K, Kraemer J, Kruger S, Loke P, McEwan P, Montalbetti C, Roberts DA, Smith M, Steinbacher S, Sujatha-Bhaskar S, Takahashi R, Wang X, Wu LC, Zhang Y, Staben ST J Med Chem. 2017 Jan 12. doi: 10.1021/acs.jmedchem.6b01363. PMID:28005357<ref>PMID:28005357</ref>
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Description:
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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<div class="pdbe-citations 5t8o" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Mitogen-activated protein kinase kinase kinase]]
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[[Category: Hymowitz, S G]]
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[[Category: McEwan, P]]
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[[Category: Smith, M A]]
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[[Category: Map3k14]]
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[[Category: Nf-kappab]]
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[[Category: Protein serine/threonine kinase]]
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[[Category: Transferase]]

Revision as of 16:37, 18 January 2017

Crystal structure of murine NF-kappaB inducing kinase (NIK) bound to Imidazobenzoxepin Compound 3

5t8o, resolution 2.41Å

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