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5wnm

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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)==
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<StructureSection load='5wnm' size='340' side='right' caption='[[5wnm]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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<StructureSection load='5wnm' size='340' side='right'caption='[[5wnm]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<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>
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<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>
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</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>
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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]] 2.6&#8491;</td></tr>
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<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>
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<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>
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<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>
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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=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>
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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/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>
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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=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>
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</table>
</table>
== Function ==
== Function ==
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[[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>
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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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>
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==See Also==
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*[[Ankyrin repeat domain-containing protein 3D structures|Ankyrin repeat domain-containing protein 3D structures]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
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</div>
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<div class="pdbe-citations 5wnm" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Lk3 transgenic mice]]
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[[Category: Large Structures]]
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Mus musculus]]
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[[Category: Huang, C S]]
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[[Category: Huang CS]]
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[[Category: Hymowitz, S G]]
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[[Category: Hymowitz SG]]
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[[Category: Complex]]
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[[Category: Inhibitor]]
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[[Category: Kinase]]
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[[Category: Transferase]]
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[[Category: Transferase-transferase inhibitor complex]]
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Current revision

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

PDB ID 5wnm

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