5e7r: Difference between revisions

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'''Unreleased structure'''


The entry 5e7r is ON HOLD until Oct 13 2017
==Crystal structure of TL10-81 bound to TAK1-TAB1==
 
<StructureSection load='5e7r' size='340' side='right' caption='[[5e7r]], [[Resolution|resolution]] 2.11&Aring;' scene=''>
Authors:  
== Structural highlights ==
 
<table><tr><td colspan='2'>[[5e7r]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E7R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E7R FirstGlance]. <br>
Description:  
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5KW:2-CHLORO-N-{2-[(5-CHLORO-2-{[4-(4-METHYLPIPERAZIN-1-YL)PHENYL]AMINO}PYRIMIDIN-4-YL)OXY]PHENYL}ACETAMIDE'>5KW</scene></td></tr>
[[Category: Unreleased Structures]]
<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=5e7r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e7r OCA], [http://pdbe.org/5e7r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e7r RCSB], [http://www.ebi.ac.uk/pdbsum/5e7r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5e7r ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/M3K7_HUMAN M3K7_HUMAN]] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs, c-jun N-terminal kinases (JNKs) and I-kappa-B kinase complex (IKK). Both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1), while nuclear factor-kappa B is activated by IKK. MAP3K7 activates also IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and mediates BMP2-induced apoptosis. In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B. Promotes TRIM5 capsid-specific restriction activity.<ref>PMID:8663074</ref> <ref>PMID:9079627</ref> <ref>PMID:10094049</ref> <ref>PMID:11460167</ref> <ref>PMID:12589052</ref> <ref>PMID:16845370</ref> <ref>PMID:16893890</ref> <ref>PMID:21512573</ref>  
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Mitogen-activated protein kinase kinase kinase]]
[[Category: Chen, Z]]
[[Category: Gurbani, D]]
[[Category: Hunter, J C]]
[[Category: Tan, L]]
[[Category: Westover, K D]]
[[Category: Mitogen-activated protein kinase kinase kinase 7/tgf-beta-activated kinase 1 and map3k7-binding protein 1]]
[[Category: Transferase-transferase inhibitor complex]]

Revision as of 16:48, 21 September 2016

Crystal structure of TL10-81 bound to TAK1-TAB1Crystal structure of TL10-81 bound to TAK1-TAB1

Structural highlights

5e7r is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Activity:Mitogen-activated protein kinase kinase kinase, with EC number 2.7.11.25
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[M3K7_HUMAN] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs, c-jun N-terminal kinases (JNKs) and I-kappa-B kinase complex (IKK). Both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1), while nuclear factor-kappa B is activated by IKK. MAP3K7 activates also IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and mediates BMP2-induced apoptosis. In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B. Promotes TRIM5 capsid-specific restriction activity.[1] [2] [3] [4] [5] [6] [7] [8]

References

  1. ↑ Moriguchi T, Kuroyanagi N, Yamaguchi K, Gotoh Y, Irie K, Kano T, Shirakabe K, Muro Y, Shibuya H, Matsumoto K, Nishida E, Hagiwara M. A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3. J Biol Chem. 1996 Jun 7;271(23):13675-9. PMID:8663074
  2. ↑ Shirakabe K, Yamaguchi K, Shibuya H, Irie K, Matsuda S, Moriguchi T, Gotoh Y, Matsumoto K, Nishida E. TAK1 mediates the ceramide signaling to stress-activated protein kinase/c-Jun N-terminal kinase. J Biol Chem. 1997 Mar 28;272(13):8141-4. PMID:9079627
  3. ↑ Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K. The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature. 1999 Mar 18;398(6724):252-6. PMID:10094049 doi:10.1038/18465
  4. ↑ Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature. 2001 Jul 19;412(6844):346-51. PMID:11460167 doi:10.1038/35085597
  5. ↑ Edlund S, Bu S, Schuster N, Aspenstrom P, Heuchel R, Heldin NE, ten Dijke P, Heldin CH, Landstrom M. Transforming growth factor-beta1 (TGF-beta)-induced apoptosis of prostate cancer cells involves Smad7-dependent activation of p38 by TGF-beta-activated kinase 1 and mitogen-activated protein kinase kinase 3. Mol Biol Cell. 2003 Feb;14(2):529-44. PMID:12589052 doi:10.1091/mbc.02-03-0037
  6. ↑ Thiefes A, Wolf A, Doerrie A, Grassl GA, Matsumoto K, Autenrieth I, Bohn E, Sakurai H, Niedenthal R, Resch K, Kracht M. The Yersinia enterocolitica effector YopP inhibits host cell signalling by inactivating the protein kinase TAK1 in the IL-1 signalling pathway. EMBO Rep. 2006 Aug;7(8):838-44. Epub 2006 Jul 14. PMID:16845370 doi:10.1038/sj.embor.7400754
  7. ↑ Huangfu WC, Omori E, Akira S, Matsumoto K, Ninomiya-Tsuji J. Osmotic stress activates the TAK1-JNK pathway while blocking TAK1-mediated NF-kappaB activation: TAO2 regulates TAK1 pathways. J Biol Chem. 2006 Sep 29;281(39):28802-10. Epub 2006 Aug 7. PMID:16893890 doi:10.1074/jbc.M603627200
  8. ↑ Pertel T, Hausmann S, Morger D, Zuger S, Guerra J, Lascano J, Reinhard C, Santoni FA, Uchil PD, Chatel L, Bisiaux A, Albert ML, Strambio-De-Castillia C, Mothes W, Pizzato M, Grutter MG, Luban J. TRIM5 is an innate immune sensor for the retrovirus capsid lattice. Nature. 2011 Apr 21;472(7343):361-5. doi: 10.1038/nature09976. PMID:21512573 doi:10.1038/nature09976

5e7r, resolution 2.11Å

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