9lfu: Difference between revisions

Latest revision as of 18:09, 7 May 2025

Crystal structure of human RIP3 kinase domain complexed with LK01003

Structural highlights

9lfu is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.93Å
Ligands:	A1D97
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RIPK3_HUMAN Essential for necroptosis, a programmed cell death process in response to death-inducing TNF-alpha family members. Upon induction of necrosis, RIPK3 interacts with, and phosphorylates RIPK1 and MLKL to form a necrosis-inducing complex. RIPK3 binds to and enhances the activity of three metabolic enzymes: GLUL, GLUD1, and PYGL. These metabolic enzymes may eventually stimulate the tricarboxylic acid cycle and oxidative phosphorylation, which could result in enhanced ROS production.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

References

↑ Zhang DW, Shao J, Lin J, Zhang N, Lu BJ, Lin SC, Dong MQ, Han J. RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science. 2009 Jul 17;325(5938):332-6. doi: 10.1126/science.1172308. Epub 2009 Jun, 4. PMID:19498109 doi:https://dx.doi.org/10.1126/science.1172308
↑ He S, Wang L, Miao L, Wang T, Du F, Zhao L, Wang X. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell. 2009 Jun 12;137(6):1100-11. doi: 10.1016/j.cell.2009.05.021. PMID:19524512 doi:10.1016/j.cell.2009.05.021
↑ Cho YS, Challa S, Moquin D, Genga R, Ray TD, Guildford M, Chan FK. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell. 2009 Jun 12;137(6):1112-23. doi: 10.1016/j.cell.2009.05.037. PMID:19524513 doi:10.1016/j.cell.2009.05.037
↑ Sun L, Wang H, Wang Z, He S, Chen S, Liao D, Wang L, Yan J, Liu W, Lei X, Wang X. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell. 2012 Jan 20;148(1-2):213-27. doi: 10.1016/j.cell.2011.11.031. PMID:22265413 doi:https://dx.doi.org/10.1016/j.cell.2011.11.031
↑ Wang Z, Jiang H, Chen S, Du F, Wang X. The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. Cell. 2012 Jan 20;148(1-2):228-43. doi: 10.1016/j.cell.2011.11.030. PMID:22265414 doi:https://dx.doi.org/10.1016/j.cell.2011.11.030
↑ Zhao J, Jitkaew S, Cai Z, Choksi S, Li Q, Luo J, Liu ZG. Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis. Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):5322-7. doi:, 10.1073/pnas.1200012109. Epub 2012 Mar 15. PMID:22421439 doi:https://dx.doi.org/10.1073/pnas.1200012109

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Zhang DW, Shao J, Lin J, Zhang N, Lu BJ, Lin SC, Dong MQ, Han J. RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science. 2009 Jul 17;325(5938):332-6. doi: 10.1126/science.1172308. Epub 2009 Jun, 4. PMID:19498109 doi:https://dx.doi.org/10.1126/science.1172308

[2] He S, Wang L, Miao L, Wang T, Du F, Zhao L, Wang X. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell. 2009 Jun 12;137(6):1100-11. doi: 10.1016/j.cell.2009.05.021. PMID:19524512 doi:10.1016/j.cell.2009.05.021

[3] Cho YS, Challa S, Moquin D, Genga R, Ray TD, Guildford M, Chan FK. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell. 2009 Jun 12;137(6):1112-23. doi: 10.1016/j.cell.2009.05.037. PMID:19524513 doi:10.1016/j.cell.2009.05.037

[4] Sun L, Wang H, Wang Z, He S, Chen S, Liao D, Wang L, Yan J, Liu W, Lei X, Wang X. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell. 2012 Jan 20;148(1-2):213-27. doi: 10.1016/j.cell.2011.11.031. PMID:22265413 doi:https://dx.doi.org/10.1016/j.cell.2011.11.031

[5] Wang Z, Jiang H, Chen S, Du F, Wang X. The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. Cell. 2012 Jan 20;148(1-2):228-43. doi: 10.1016/j.cell.2011.11.030. PMID:22265414 doi:https://dx.doi.org/10.1016/j.cell.2011.11.030

[6] Zhao J, Jitkaew S, Cai Z, Choksi S, Li Q, Luo J, Liu ZG. Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis. Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):5322-7. doi:, 10.1073/pnas.1200012109. Epub 2012 Mar 15. PMID:22421439 doi:https://dx.doi.org/10.1073/pnas.1200012109

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9lfu is ON HOLD  until Paper Publication
+==Crystal structure of human RIP3 kinase domain complexed with LK01003==
+<StructureSection load='9lfu' size='340' side='right'caption='[[9lfu]], [[Resolution|resolution]] 2.93&Aring;' scene=''>
-Authors: Xie, H., Su, H.X., Li, M.J., Xu, Y.C.
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9lfu]] 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=9LFU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9LFU FirstGlance]. <br>
-Description: Crystal structure of human RIP3 kinase domain complexed with LK01003
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.93&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1D97:2-cyclopentyl-~{N}-(6-propan-2-ylsulfonylquinolin-4-yl)-1,3-benzothiazol-5-amine'>A1D97</scene></td></tr>
-[[Category: Li, M.J]]
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9lfu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9lfu OCA], [https://pdbe.org/9lfu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9lfu RCSB], [https://www.ebi.ac.uk/pdbsum/9lfu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9lfu ProSAT]</span></td></tr>
-[[Category: Xu, Y.C]]
+</table>
-[[Category: Xie, H]]
+== Function ==
-[[Category: Su, H.X]]
+[https://www.uniprot.org/uniprot/RIPK3_HUMAN RIPK3_HUMAN] Essential for necroptosis, a programmed cell death process in response to death-inducing TNF-alpha family members. Upon induction of necrosis, RIPK3 interacts with, and phosphorylates RIPK1 and MLKL to form a necrosis-inducing complex. RIPK3 binds to and enhances the activity of three metabolic enzymes: GLUL, GLUD1, and PYGL. These metabolic enzymes may eventually stimulate the tricarboxylic acid cycle and oxidative phosphorylation, which could result in enhanced ROS production.<ref>PMID:19498109</ref> <ref>PMID:19524512</ref> <ref>PMID:19524513</ref> <ref>PMID:22265413</ref> <ref>PMID:22265414</ref> <ref>PMID:22421439</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Li MJ]]
+[[Category: Su HX]]
+[[Category: Xie H]]
+[[Category: Xu YC]]

9lfu: Difference between revisions

Latest revision as of 18:09, 7 May 2025

Crystal structure of human RIP3 kinase domain complexed with LK01003

Structural highlights

Function

References

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