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| | ==Crystal structure of murine NF-kappaB inducing kinase (NIK) bound to a 6-alkynylindoline (cmp1)== | | ==Crystal structure of murine NF-kappaB inducing kinase (NIK) bound to a 6-alkynylindoline (cmp1)== |
| - | <StructureSection load='4g3e' size='340' side='right' caption='[[4g3e]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='4g3e' size='340' side='right'caption='[[4g3e]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4g3e]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G3E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4G3E FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4g3e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G3E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G3E FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0WC:(2R)-4-[1-(2-AMINO-5-CHLOROPYRIMIDIN-4-YL)-2,3-DIHYDRO-1H-INDOL-6-YL]-2-(1,3-THIAZOL-2-YL)BUT-3-YN-2-OL'>0WC</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0WC:(2R)-4-[1-(2-AMINO-5-CHLOROPYRIMIDIN-4-YL)-2,3-DIHYDRO-1H-INDOL-6-YL]-2-(1,3-THIAZOL-2-YL)BUT-3-YN-2-OL'>0WC</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4g3c|4g3c]], [[4g3d|4g3d]], [[4g3f|4g3f]], [[4g3g|4g3g]]</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=4g3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g3e OCA], [https://pdbe.org/4g3e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g3e RCSB], [https://www.ebi.ac.uk/pdbsum/4g3e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g3e ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Map3k14, NF-kappaB inducing kinase, Nik ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
| + | |
| - | <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>
| + | |
| - | <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=4g3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g3e OCA], [http://pdbe.org/4g3e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4g3e RCSB], [http://www.ebi.ac.uk/pdbsum/4g3e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4g3e ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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> | + | [https://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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Mitogen-activated protein kinase kinase kinase]] | + | [[Category: Mus musculus]] |
| - | [[Category: Hymowitz, S G]] | + | [[Category: Hymowitz SG]] |
| - | [[Category: Leon-Boenig, G de]] | + | [[Category: De Leon-Boenig G]] |
| - | [[Category: Map3k14]]
| + | |
| - | [[Category: Nf-kappab]]
| + | |
| - | [[Category: Non-rd kinase]]
| + | |
| - | [[Category: Protein serine/threonine kinase]]
| + | |
| - | [[Category: Structure-based drug design]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Transferase-transferase inhibitor complex]]
| + | |
| Structural highlights
Function
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.[1]
Publication Abstract from PubMed
The NF-kappaB inducing kinase (NIK) regulates the non-canonical NF-kappaB pathway downstream of important clinical targets including BAFF, RANKL, and LTbeta. Despite numerous genetic studies associating dysregulation of this pathway with autoimmune diseases and hematological cancers, detailed molecular characterization of this central signaling node has been lacking. We undertook a systematic cloning and expression effort to generate soluble, well-behaved proteins encompassing the kinase domains of human and murine NIK. Structures of the apo NIK kinase domain from both species reveal an active-like conformation in the absence of phosphorylation. ATP consumption and peptide phosphorylation assays confirm that phosphorylation of NIK does not increase enzymatic activity. Structures of murine NIK bound to inhibitors possessing two different chemotypes reveal conformational flexibility in the gatekeeper residue controlling access to a hydrophobic pocket. Finally, a single amino acid difference affects the ability of some inhibitors to bind murine and human NIK with the same affinity.
The crystal structure of the catalytic domain of the NF-kappaB inducing kinase reveals a narrow but flexible active site.,de Leon-Boenig G, Bowman KK, Feng JA, Crawford T, Everett C, Franke Y, Oh A, Stanley M, Staben ST, Starovasnik MA, Wallweber HJ, Wu J, Wu LC, Johnson AR, Hymowitz SG Structure. 2012 Oct 10;20(10):1704-14. doi: 10.1016/j.str.2012.07.013. Epub 2012 , Aug 23. PMID:22921830[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Xiao G, Harhaj EW, Sun SC. NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100. Mol Cell. 2001 Feb;7(2):401-9. PMID:11239468
- ↑ de Leon-Boenig G, Bowman KK, Feng JA, Crawford T, Everett C, Franke Y, Oh A, Stanley M, Staben ST, Starovasnik MA, Wallweber HJ, Wu J, Wu LC, Johnson AR, Hymowitz SG. The crystal structure of the catalytic domain of the NF-kappaB inducing kinase reveals a narrow but flexible active site. Structure. 2012 Oct 10;20(10):1704-14. doi: 10.1016/j.str.2012.07.013. Epub 2012 , Aug 23. PMID:22921830 doi:http://dx.doi.org/10.1016/j.str.2012.07.013
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