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==Crystal structure of murine receptor-interacting protein 4 (Ripk4) D143N bound to tozasertib (VX-680)==
==Crystal structure of murine receptor-interacting protein 4 (Ripk4) D143N bound to tozasertib (VX-680)==
<StructureSection load='5wnm' size='340' side='right' caption='[[5wnm]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
<StructureSection load='5wnm' size='340' side='right'caption='[[5wnm]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5wnm]] is a 1 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=5WNM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WNM FirstGlance]. <br>
<table><tr><td colspan='2'>[[5wnm]] is a 1 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=5WNM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WNM FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=VX6:CYCLOPROPANECARBOXYLIC+ACID+{4-[4-(4-METHYL-PIPERAZIN-1-YL)-6-(5-METHYL-2H-PYRAZOL-3-YLAMINO)-PYRIMIDIN-2-YLSULFANYL]-PHENYL}-AMIDE'>VX6</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5wni|5wni]], [[5wnj|5wnj]], [[5wnk|5wnk]], [[5wnl|5wnl]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=VX6:CYCLOPROPANECARBOXYLIC+ACID+{4-[4-(4-METHYL-PIPERAZIN-1-YL)-6-(5-METHYL-2H-PYRAZOL-3-YLAMINO)-PYRIMIDIN-2-YLSULFANYL]-PHENYL}-AMIDE'>VX6</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ripk4, Ankrd3, Pkk ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=5wnm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wnm OCA], [https://pdbe.org/5wnm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wnm RCSB], [https://www.ebi.ac.uk/pdbsum/5wnm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wnm ProSAT]</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=5wnm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wnm OCA], [http://pdbe.org/5wnm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wnm RCSB], [http://www.ebi.ac.uk/pdbsum/5wnm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wnm ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/RIPK4_MOUSE RIPK4_MOUSE]] Involved in stratified epithelial development (By similarity). It is a direct transcriptional target of TP63. Plays a role in NF-kappa-B activation.<ref>PMID:12446564</ref> <ref>PMID:22197488</ref>
[https://www.uniprot.org/uniprot/RIPK4_MOUSE RIPK4_MOUSE] Involved in stratified epithelial development (By similarity). It is a direct transcriptional target of TP63. Plays a role in NF-kappa-B activation.<ref>PMID:12446564</ref> <ref>PMID:22197488</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Receptor-interacting protein kinase 4 (RIPK4) is a highly conserved regulator of epidermal differentiation. Members of the RIPK family possess a common kinase domain as well as unique accessory domains that likely dictate subcellular localization and substrate preferences. Mutations in human RIPK4 manifest as Bartsocas-Papas syndrome (BPS), a genetic disorder characterized by severe craniofacial and limb abnormalities. We describe the structure of the murine Ripk4 (MmRipk4) kinase domain, in ATP- and inhibitor-bound forms. The crystallographic dimer of MmRipk4 is similar to those of RIPK2 and BRAF, and we show that the intact dimeric entity is required for MmRipk4 catalytic activity through a series of engineered mutations and cell-based assays. We also assess the impact of BPS mutations on protein structure and activity to elucidate the molecular origins of the disease.


Crystal Structure of Ripk4 Reveals Dimerization-Dependent Kinase Activity.,Huang CS, Oberbeck N, Hsiao YC, Liu P, Johnson AR, Dixit VM, Hymowitz SG Structure. 2018 May 1;26(5):767-777.e5. doi: 10.1016/j.str.2018.04.002. Epub 2018, Apr 26. PMID:29706531<ref>PMID:29706531</ref>
==See Also==
 
*[[Ankyrin repeat domain-containing protein 3D structures|Ankyrin repeat domain-containing protein 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
</div>
<div class="pdbe-citations 5wnm" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Lk3 transgenic mice]]
[[Category: Large Structures]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Mus musculus]]
[[Category: Huang, C S]]
[[Category: Huang CS]]
[[Category: Hymowitz, S G]]
[[Category: Hymowitz SG]]
[[Category: Complex]]
[[Category: Inhibitor]]
[[Category: Kinase]]
[[Category: Transferase]]
[[Category: Transferase-transferase inhibitor complex]]

Latest revision as of 17:16, 13 March 2024

Crystal structure of murine receptor-interacting protein 4 (Ripk4) D143N bound to tozasertib (VX-680)Crystal structure of murine receptor-interacting protein 4 (Ripk4) D143N bound to tozasertib (VX-680)

Structural highlights

5wnm is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.6Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RIPK4_MOUSE Involved in stratified epithelial development (By similarity). It is a direct transcriptional target of TP63. Plays a role in NF-kappa-B activation.[1] [2]

See Also

References

  1. ↑ Meylan E, Martinon F, Thome M, Gschwendt M, Tschopp J. RIP4 (DIK/PKK), a novel member of the RIP kinase family, activates NF-kappa B and is processed during apoptosis. EMBO Rep. 2002 Dec;3(12):1201-8. doi: 10.1093/embo-reports/kvf236. Epub 2002 Nov , 21. PMID:12446564 doi:http://dx.doi.org/10.1093/embo-reports/kvf236
  2. ↑ Mitchell K, O'Sullivan J, Missero C, Blair E, Richardson R, Anderson B, Antonini D, Murray JC, Shanske AL, Schutte BC, Romano RA, Sinha S, Bhaskar SS, Black GC, Dixon J, Dixon MJ. Exome sequence identifies RIPK4 as the Bartsocas-Papas syndrome locus. Am J Hum Genet. 2012 Jan 13;90(1):69-75. doi: 10.1016/j.ajhg.2011.11.013. Epub, 2011 Dec 22. PMID:22197488 doi:10.1016/j.ajhg.2011.11.013

5wnm, resolution 2.60Å

Drag the structure with the mouse to rotate

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