2hko

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[[Image:2hko.gif|left|200px]]
 
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{{Structure
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==Crystal structure of LSD1==
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|PDB= 2hko |SIZE=350|CAPTION= <scene name='initialview01'>2hko</scene>, resolution 2.80&Aring;
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<StructureSection load='2hko' size='340' side='right'caption='[[2hko]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=FAD:FLAVIN-ADENINE DINUCLEOTIDE'>FAD</scene>
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<table><tr><td colspan='2'>[[2hko]] is a 1 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=2HKO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HKO FirstGlance]. <br>
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|ACTIVITY=
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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]] 2.8&#8491;</td></tr>
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|GENE= AOF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr>
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}}
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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=2hko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hko OCA], [https://pdbe.org/2hko PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hko RCSB], [https://www.ebi.ac.uk/pdbsum/2hko PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hko 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/hk/2hko_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2hko ConSurf].
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<div style="clear:both"></div>
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'''Crystal structure of LSD1'''
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==See Also==
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*[[Lysine-specific histone demethylase 3D structures|Lysine-specific histone demethylase 3D structures]]
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== References ==
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==Overview==
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<references/>
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Lysine-specific demethylase 1 (LSD1) was recently identified as the first histone demethylase that specifically demethylates monomethylated and dimethylated histone H3 at K4. It is a component of the CoREST and other corepressor complexes and plays an important role in silencing neuronal-specific genes in nonneuronal cells, but the molecular mechanisms of its action remain unclear. The 2.8-A-resolution crystal structure of the human LSD1 reveals that LSD1 defines a new subfamily of FAD-dependent oxidases. The active center of LSD1 is characterized by a remarkable 1,245-A3 substrate-binding cavity with a highly negative electrostatic potential. Although the protein core of LSD1 resembles other flavoenzymes, its enzymatic activity and functions require two additional structural modules: an N-terminal SWIRM domain important for protein stability and a large insertion in the catalytic domain indispensable both for the demethylase activity and the interaction with CoREST. These results provide a framework for further probing the catalytic mechanism and the functional roles of LSD1.
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__TOC__
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</StructureSection>
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==About this Structure==
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2HKO is a [[Single protein]] structure of 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=2HKO OCA].
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==Reference==
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Crystal structure of human histone lysine-specific demethylase 1 (LSD1)., Chen Y, Yang Y, Wang F, Wan K, Yamane K, Zhang Y, Lei M, Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):13956-61. Epub 2006 Sep 6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16956976 16956976]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Chen, Y.]]
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[[Category: Chen Y]]
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[[Category: Lei, M.]]
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[[Category: Lei M]]
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[[Category: Wang, F.]]
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[[Category: Wang F]]
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[[Category: Yanane, K.]]
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[[Category: Yanane K]]
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[[Category: Yang, Y T.]]
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[[Category: Yang YT]]
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[[Category: Zhang, Y.]]
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[[Category: Zhang Y]]
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[[Category: FAD]]
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[[Category: amine oxidase domain]]
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[[Category: coiled-coil]]
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[[Category: fad binding domain]]
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[[Category: swirm domain]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:18:16 2008''
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Current revision

Crystal structure of LSD1

PDB ID 2hko

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