2hko: Difference between revisions

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-[[Image:2hko.gif|left|200px]]<br />
-<applet load="2hko" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="2hko, resolution 2.80&Aring;" />
-'''Crystal structure of LSD1'''<br />
-==Overview==
+==Crystal structure of LSD1==
-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.
+<StructureSection load='2hko' size='340' side='right'caption='[[2hko]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+== Structural highlights ==
+<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>
+</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>
+<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>
+<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>
+</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/hk/2hko_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2hko ConSurf].
+<div style="clear:both"></div>
-==About this Structure==
+==See Also==
-HKO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with FAD as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2HKO OCA].
+*[[Lysine-specific histone demethylase 3D structures|Lysine-specific histone demethylase 3D structures]]
+== References ==
-==Reference==
+<references/>
-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://ispc.weizmann.ac.il//pmbin/getpm?pmid=16956976 16956976]
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Chen, Y.]]
+[[Category: Chen Y]]
-[[Category: Lei, M.]]
+[[Category: Lei M]]
-[[Category: Wang, F.]]
+[[Category: Wang F]]
-[[Category: Yanane, K.]]
+[[Category: Yanane K]]
-[[Category: Yang, Y.T.]]
+[[Category: Yang YT]]
-[[Category: Zhang, Y.]]
+[[Category: Zhang Y]]
-[[Category: FAD]]
-[[Category: amine oxidase domain]]
-[[Category: coiled-coil]]
-[[Category: fad binding domain]]
-[[Category: swirm domain]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:33:30 2007''