4kik

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{{STRUCTURE_4kik| PDB=4kik | SCENE= }}
 
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===Human IkB kinase beta===
 
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==Function==
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==Human IkB kinase beta==
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[[http://www.uniprot.org/uniprot/IKKB_HUMAN IKKB_HUMAN]] Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation.<ref>PMID:11297557</ref> <ref>PMID:17213322</ref> <ref>PMID:20434986</ref> <ref>PMID:20410276</ref> <ref>PMID:20797629</ref> <ref>PMID:21138416</ref>
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<StructureSection load='4kik' size='340' side='right'caption='[[4kik]], [[Resolution|resolution]] 2.83&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4kik]] is a 2 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=4KIK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KIK FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.83&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KSA:K-252A'>KSA</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4kik FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kik OCA], [https://pdbe.org/4kik PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kik RCSB], [https://www.ebi.ac.uk/pdbsum/4kik PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kik ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/IKKB_HUMAN IKKB_HUMAN] Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation.<ref>PMID:11297557</ref> <ref>PMID:17213322</ref> <ref>PMID:20434986</ref> <ref>PMID:20410276</ref> <ref>PMID:20797629</ref> <ref>PMID:21138416</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Phosphorylation of inhibitor of nuclear transcription factor kappaB (IkappaB) by IkappaB kinase (IKK) triggers the degradation of IkappaB and migration of cytoplasmic kappaB to the nucleus where it promotes the transcription of its target genes. Activation of IKK is achieved by phosphorylation of its main subunit, IKKbeta, at the activation loop sites. Here, we report the 2.8 A resolution crystal structure of human IKKbeta (hIKKbeta), which is partially phosphorylated and bound to the staurosporine analog K252a. The hIKKbeta protomer adopts a trimodular structure that closely resembles that from Xenopus laevis (xIKKbeta): an N-terminal kinase domain (KD), a central ubiquitin-like domain (ULD), and a C-terminal scaffold/dimerization domain (SDD). Although hIKKbeta and xIKKbeta utilize a similar dimerization mode, their overall geometries are distinct. In contrast to the structure resembling closed shears reported previously for xIKKbeta, hIKKbeta exists as an open asymmetric dimer in which the two KDs are further apart, with one in an active and the other in an inactive conformation. Dimer interactions are limited to the C-terminal six-helix bundle that acts as a hinge between the two subunits. The observed domain movements in the structures of IKKbeta may represent trans-phosphorylation steps that accompany IKKbeta activation.
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==About this Structure==
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Crystal Structure of a Human IkappaB Kinase beta Asymmetric Dimer.,Liu S, Misquitta YR, Olland A, Johnson MA, Kelleher KS, Kriz R, Lin LL, Stahl M, Mosyak L J Biol Chem. 2013 Aug 2;288(31):22758-67. doi: 10.1074/jbc.M113.482596. Epub 2013, Jun 21. PMID:23792959<ref>PMID:23792959</ref>
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[[4kik]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Rhizobium_loessense Rhizobium loessense]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KIK OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<references group="xtra"/><references/>
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</div>
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<div class="pdbe-citations 4kik" 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>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: I-kappa-B kinase]]
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[[Category: Large Structures]]
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[[Category: Rhizobium loessense]]
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[[Category: Liu S]]
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[[Category: Liu, S.]]
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[[Category: Mosyak L]]
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[[Category: Mosyak, L.]]
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[[Category: Kinase]]
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[[Category: Nkb signaling]]
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[[Category: Transferase]]
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Current revision

Human IkB kinase beta

PDB ID 4kik

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