3lj2

From Proteopedia

(Difference between revisions)

Current revision

IRE1 complexed with JAK Inhibitor I

Structural highlights

3lj2 is a 2 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.33Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IRE1_YEAST Senses unfolded proteins in the lumen of the endoplasmic reticulum via its N-terminal domain which leads to enzyme auto-activation. The active endoribonuclease domain splices HAC1 precursor mRNA to produce the mature form which then induces transcription of UPR target genes.^[1] ^[2] ^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Signaling in the most conserved branch of the endoplasmic reticulum (ER) unfolded protein response (UPR) is initiated by sequence-specific cleavage of the HAC1/XBP1 mRNA by the ER stress-induced kinase-endonuclease IRE1. We have discovered that the flavonol quercetin activates yeast IRE1's RNase and potentiates activation by ADP, a natural activating ligand that engages the IRE1 nucleotide-binding cleft. Enzyme kinetics and the structure of a cocrystal of IRE1 complexed with ADP and quercetin reveal engagement by quercetin of an unanticipated ligand-binding pocket at the dimer interface of IRE1's kinase extension nuclease (KEN) domain. Analytical ultracentrifugation and crosslinking studies support the preeminence of enhanced dimer formation in quercetin's mechanism of action. These findings hint at the existence of endogenous cytoplasmic ligands that may function alongside stress signals from the ER lumen to modulate IRE1 activity and at the potential for the development of drugs that modify UPR signaling from this unanticipated site.

Flavonol activation defines an unanticipated ligand-binding site in the kinase-RNase domain of IRE1.,Wiseman RL, Zhang Y, Lee KP, Harding HP, Haynes CM, Price J, Sicheri F, Ron D Mol Cell. 2010 Apr 23;38(2):291-304. PMID:20417606^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Welihinda AA, Kaufman RJ. The unfolded protein response pathway in Saccharomyces cerevisiae. Oligomerization and trans-phosphorylation of Ire1p (Ern1p) are required for kinase activation. J Biol Chem. 1996 Jul 26;271(30):18181-7. PMID:8663458
↑ Shamu CE, Walter P. Oligomerization and phosphorylation of the Ire1p kinase during intracellular signaling from the endoplasmic reticulum to the nucleus. EMBO J. 1996 Jun 17;15(12):3028-39. PMID:8670804
↑ Sidrauski C, Walter P. The transmembrane kinase Ire1p is a site-specific endonuclease that initiates mRNA splicing in the unfolded protein response. Cell. 1997 Sep 19;90(6):1031-9. PMID:9323131
↑ Wiseman RL, Zhang Y, Lee KP, Harding HP, Haynes CM, Price J, Sicheri F, Ron D. Flavonol activation defines an unanticipated ligand-binding site in the kinase-RNase domain of IRE1. Mol Cell. 2010 Apr 23;38(2):291-304. PMID:20417606 doi:10.1016/j.molcel.2010.04.001

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3lj2"

Categories: Large Structures | Saccharomyces cerevisiae | Lee KPK | Sicheri F

@@ Line 1: / Line 1: @@
 ==IRE1 complexed with JAK Inhibitor I==
-<StructureSection load='3lj2' size='340' side='right' caption='[[3lj2]], [[Resolution|resolution]] 3.33&Aring;' scene=''>
+<StructureSection load='3lj2' size='340' side='right'caption='[[3lj2]], [[Resolution|resolution]] 3.33&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3lj2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LJ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LJ2 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3lj2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LJ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LJ2 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IZA:2-TERT-BUTYL-9-FLUORO-3,6-DIHYDRO-7H-BENZ[H]-IMIDAZ[4,5-F]ISOQUINOLINE-7-ONE'>IZA</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]] 3.33&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IZA:2-TERT-BUTYL-9-FLUORO-3,6-DIHYDRO-7H-BENZ[H]-IMIDAZ[4,5-F]ISOQUINOLINE-7-ONE'>IZA</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3lj0|3lj0]], [[3lj1|3lj1]]</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=3lj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lj2 OCA], [https://pdbe.org/3lj2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lj2 RCSB], [https://www.ebi.ac.uk/pdbsum/3lj2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lj2 ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ERN1, IRE1, YHR079C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</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=3lj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lj2 OCA], [http://pdbe.org/3lj2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lj2 RCSB], [http://www.ebi.ac.uk/pdbsum/3lj2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lj2 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/IRE1_YEAST IRE1_YEAST]] Senses unfolded proteins in the lumen of the endoplasmic reticulum via its N-terminal domain which leads to enzyme auto-activation. The active endoribonuclease domain splices HAC1 precursor mRNA to produce the mature form which then induces transcription of UPR target genes.<ref>PMID:8663458</ref> <ref>PMID:8670804</ref> <ref>PMID:9323131</ref>
+[https://www.uniprot.org/uniprot/IRE1_YEAST IRE1_YEAST] Senses unfolded proteins in the lumen of the endoplasmic reticulum via its N-terminal domain which leads to enzyme auto-activation. The active endoribonuclease domain splices HAC1 precursor mRNA to produce the mature form which then induces transcription of UPR target genes.<ref>PMID:8663458</ref> <ref>PMID:8670804</ref> <ref>PMID:9323131</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lj/3lj2_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lj/3lj2_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
@@ Line 38: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Atcc 18824]]
+[[Category: Large Structures]]
-[[Category: Lee, K P.K]]
+[[Category: Saccharomyces cerevisiae]]
-[[Category: Sicheri, F]]
+[[Category: Lee KPK]]
-[[Category: Atp-binding]]
+[[Category: Sicheri F]]
-[[Category: Endoplasmic reticulum]]
-[[Category: Glycoprotein]]
-[[Category: Hydrolase]]
-[[Category: Kinase]]
-[[Category: Kinase inhibitor]]
-[[Category: Magnesium]]
-[[Category: Membrane]]
-[[Category: Metal-binding]]
-[[Category: Multifunctional enzyme]]
-[[Category: Nuclease activator]]
-[[Category: Nucleotide-binding]]
-[[Category: Phosphoprotein]]
-[[Category: Serine/threonine-protein kinase]]
-[[Category: Transcription]]
-[[Category: Transcription regulation]]
-[[Category: Transferase]]
-[[Category: Transmembrane]]
-[[Category: Unfolded protein response]]

3lj2

From Proteopedia

Current revision

IRE1 complexed with JAK Inhibitor I

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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