4uv8: Difference between revisions
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==LSD1(KDM1A)-CoREST in complex with 1-Benzyl-Tranylcypromine== | ==LSD1(KDM1A)-CoREST in complex with 1-Benzyl-Tranylcypromine== | ||
<StructureSection load='4uv8' size='340' side='right' caption='[[4uv8]], [[Resolution|resolution]] 2.80Å' scene=''> | <StructureSection load='4uv8' size='340' side='right'caption='[[4uv8]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4uv8]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UV8 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4uv8]] is a 2 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=4UV8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UV8 FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=D69:[[(2R,3S,4S)-5-[(4AS,10AS)-4A-[(1S)-3-AZANYLIDENE-1,4-DIPHENYL-BUTYL]-7,8-DIMETHYL-2,4-BIS(OXIDANYLIDENE)-5,10A-DIHYDRO-1H-BENZO[G]PTERIDIN-10-YL]-2,3,4-TRIS(OXIDANYL)PENTOXY]-OXIDANYL-PHOSPHORYL]+[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-BIS(OXIDANYL)OXOLAN-2-YL]METHYL+HYDROGEN+PHOSPHATE'>D69</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D69:[[(2R,3S,4S)-5-[(4AS,10AS)-4A-[(1S)-3-AZANYLIDENE-1,4-DIPHENYL-BUTYL]-7,8-DIMETHYL-2,4-BIS(OXIDANYLIDENE)-5,10A-DIHYDRO-1H-BENZO[G]PTERIDIN-10-YL]-2,3,4-TRIS(OXIDANYL)PENTOXY]-OXIDANYL-PHOSPHORYL]+[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-BIS(OXIDANYL)OXOLAN-2-YL]METHYL+HYDROGEN+PHOSPHATE'>D69</scene></td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4uv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uv8 OCA], [https://pdbe.org/4uv8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uv8 RCSB], [https://www.ebi.ac.uk/pdbsum/4uv8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uv8 ProSAT]</span></td></tr> | ||
<table> | </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> | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4uv8" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Lysine-specific histone demethylase 3D structures|Lysine-specific histone demethylase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Botrugno | [[Category: Homo sapiens]] | ||
[[Category: Cappa | [[Category: Large Structures]] | ||
[[Category: Ciossani | [[Category: Botrugno O]] | ||
[[Category: Dessanti | [[Category: Cappa A]] | ||
[[Category: Mai | [[Category: Ciossani G]] | ||
[[Category: Mattevi | [[Category: Dessanti P]] | ||
[[Category: Mercurio | [[Category: Mai A]] | ||
[[Category: Meroni | [[Category: Mattevi A]] | ||
[[Category: Minucci | [[Category: Mercurio C]] | ||
[[Category: Thaler | [[Category: Meroni G]] | ||
[[Category: Tortorici | [[Category: Minucci S]] | ||
[[Category: Trifiro | [[Category: Thaler F]] | ||
[[Category: Valente | [[Category: Tortorici M]] | ||
[[Category: Varasi | [[Category: Trifiro P]] | ||
[[Category: Vianello | [[Category: Valente S]] | ||
[[Category: Villa | [[Category: Varasi M]] | ||
[[Category: Vianello P]] | |||
[[Category: Villa M]] | |||