2uxn

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{{Seed}}
 
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[[Image:2uxn.png|left|200px]]
 
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==Structural Basis of Histone Demethylation by LSD1 Revealed by Suicide Inactivation==
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The line below this paragraph, containing "STRUCTURE_2uxn", creates the "Structure Box" on the page.
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<StructureSection load='2uxn' size='340' side='right'caption='[[2uxn]], [[Resolution|resolution]] 2.72&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2uxn]] is a 3 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=2UXN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2UXN FirstGlance]. <br>
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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]] 2.72&#8491;</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=FDA:DIHYDROFLAVINE-ADENINE+DINUCLEOTIDE'>FDA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LYP:N~6~-METHYL-N~6~-PROPYL-L-LYSINE'>LYP</scene></td></tr>
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{{STRUCTURE_2uxn| PDB=2uxn | SCENE= }}
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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=2uxn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uxn OCA], [https://pdbe.org/2uxn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2uxn RCSB], [https://www.ebi.ac.uk/pdbsum/2uxn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2uxn ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/KDM1A_HUMAN KDM1A_HUMAN] Histone demethylase that demethylates both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me. May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity. Also acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in ANDR-containing complexes, which mediates phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag that prevents demethylation H3K4me, prevents H3K4me demethylase activity of KDM1A. Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation. Demethylates and stabilizes the DNA methylase DNMT1. Required for gastrulation during embryogenesis. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development.<ref>PMID:12032298</ref> <ref>PMID:15620353</ref> <ref>PMID:16079795</ref> <ref>PMID:17805299</ref> <ref>PMID:20228790</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ux/2uxn_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2uxn ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Histone methylation regulates diverse chromatin-templated processes, including transcription. The recent discovery of the first histone lysine-specific demethylase (LSD1) has changed the long-held view that histone methylation is a permanent epigenetic mark. LSD1 is a flavin adenine dinucleotide (FAD)-dependent amine oxidase that demethylates histone H3 Lys4 (H3-K4). However, the mechanism by which LSD1 achieves its substrate specificity is unclear. We report the crystal structure of human LSD1 with a propargylamine-derivatized H3 peptide covalently tethered to FAD. H3 adopts three consecutive gamma-turns, enabling an ideal side chain spacing that places its N terminus into an anionic pocket and positions methyl-Lys4 near FAD for catalysis. The LSD1 active site cannot productively accommodate more than three residues on the N-terminal side of the methyllysine, explaining its H3-K4 specificity. The unusual backbone conformation of LSD1-bound H3 suggests a strategy for designing potent LSD1 inhibitors with therapeutic potential.
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===STRUCTURAL BASIS OF HISTONE DEMETHYLATION BY LSD1 REVEALED BY SUICIDE INACTIVATION===
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Structural basis of histone demethylation by LSD1 revealed by suicide inactivation.,Yang M, Culhane JC, Szewczuk LM, Gocke CB, Brautigam CA, Tomchick DR, Machius M, Cole PA, Yu H Nat Struct Mol Biol. 2007 Jun;14(6):535-9. Epub 2007 May 27. PMID:17529991<ref>PMID:17529991</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2uxn" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_17529991}}, adds the Publication Abstract to the page
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*[[Lysine-specific histone demethylase 3D structures|Lysine-specific histone demethylase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 17529991 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_17529991}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2UXN is a 3 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UXN OCA].
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==Reference==
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<ref group="xtra">PMID:17529991</ref><ref group="xtra">PMID:16885027</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Brautigam, C A.]]
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[[Category: Large Structures]]
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[[Category: Cole, P A.]]
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[[Category: Brautigam CA]]
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[[Category: Culhane, J C.]]
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[[Category: Cole PA]]
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[[Category: Gocke, C B.]]
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[[Category: Culhane JC]]
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[[Category: Machius, M.]]
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[[Category: Gocke CB]]
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[[Category: Szewczuk, L M.]]
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[[Category: Machius M]]
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[[Category: Tomchick, D R.]]
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[[Category: Szewczuk LM]]
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[[Category: Yang, M.]]
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[[Category: Tomchick DR]]
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[[Category: Yu, H.]]
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[[Category: Yang M]]
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[[Category: Alternative splicing]]
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[[Category: Yu H]]
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[[Category: Chromatin demethylation]]
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[[Category: Chromatin regulator]]
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[[Category: Coiled coil]]
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[[Category: Corest]]
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[[Category: Fad]]
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[[Category: Histone demethylase]]
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[[Category: Host-virus interaction]]
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[[Category: Lsd1]]
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[[Category: Nuclear protein]]
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[[Category: Nucleosome]]
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[[Category: Oxidoreductase]]
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[[Category: Oxidoreductase/repressor complex]]
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[[Category: Oxidoreductase/transcription regulator]]
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[[Category: Phosphorylation]]
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[[Category: Repressor]]
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[[Category: Transcription]]
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[[Category: Transcription regulation]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Apr 19 08:06:38 2009''
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Current revision

Structural Basis of Histone Demethylation by LSD1 Revealed by Suicide Inactivation

PDB ID 2uxn

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