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[[Image:2uxn.png|left|200px]]


{{STRUCTURE_2uxn| PDB=2uxn | SCENE= }}
==Structural Basis of Histone Demethylation by LSD1 Revealed by Suicide Inactivation==
<StructureSection load='2uxn' size='340' side='right'caption='[[2uxn]], [[Resolution|resolution]] 2.72&Aring;' scene=''>
== Structural highlights ==
<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>
</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>
<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>
<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>
</table>
== Function ==
[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>
== 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/ux/2uxn_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


===STRUCTURAL BASIS OF HISTONE DEMETHYLATION BY LSD1 REVEALED BY SUICIDE INACTIVATION===
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>


{{ABSTRACT_PUBMED_17529991}}
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
==About this Structure==
<div class="pdbe-citations 2uxn" style="background-color:#fffaf0;"></div>
[[2uxn]] is a 3 chain structure of [[Lysine-specific histone demethylase 1]] with sequence 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].


==See Also==
==See Also==
*[[Lysine-specific histone demethylase 1|Lysine-specific histone demethylase 1]]
*[[Lysine-specific histone demethylase 3D structures|Lysine-specific histone demethylase 3D structures]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:017529991</ref><ref group="xtra">PMID:016885027</ref><references group="xtra"/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Brautigam, C A.]]
[[Category: Large Structures]]
[[Category: Cole, P A.]]
[[Category: Brautigam CA]]
[[Category: Culhane, J C.]]
[[Category: Cole PA]]
[[Category: Gocke, C B.]]
[[Category: Culhane JC]]
[[Category: Machius, M.]]
[[Category: Gocke CB]]
[[Category: Szewczuk, L M.]]
[[Category: Machius M]]
[[Category: Tomchick, D R.]]
[[Category: Szewczuk LM]]
[[Category: Yang, M.]]
[[Category: Tomchick DR]]
[[Category: Yu, H.]]
[[Category: Yang M]]
[[Category: Chromatin demethylation]]
[[Category: Yu H]]
[[Category: Chromatin regulator]]
[[Category: Corest]]
[[Category: Fad]]
[[Category: Histone demethylase]]
[[Category: Host-virus interaction]]
[[Category: Lsd1]]
[[Category: Nuclear protein]]
[[Category: Nucleosome]]
[[Category: Oxidoreductase]]
[[Category: Oxidoreductase-repressor complex]]
[[Category: Oxidoreductase-transcription regulator complex]]
[[Category: Phosphorylation]]
[[Category: Repressor]]
[[Category: Transcription]]
[[Category: Transcription regulation]]
Retrieved from "https://proteopedia.org/2uxn"