5lbq: Difference between revisions
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==LSD1-CoREST1 in complex with quinazoline-derivative reversible inhibitor== | |||
<StructureSection load='5lbq' size='340' side='right' caption='[[5lbq]], [[Resolution|resolution]] 3.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5lbq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LBQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LBQ FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=767:N2-(3-(DIMETHYLAMINO)PROPYL)-6,7-DIMETHOXY-N4,N4-DIMETHYLQUINAZOLINE-2,4-DIAMINE'>767</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr> | |||
[[Category: | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5lbq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lbq OCA], [http://pdbe.org/5lbq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lbq RCSB], [http://www.ebi.ac.uk/pdbsum/5lbq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lbq ProSAT]</span></td></tr> | ||
</table> | |||
== Function == | |||
[[http://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> [[http://www.uniprot.org/uniprot/RCOR1_HUMAN RCOR1_HUMAN]] Essential component of the BHC complex, a corepressor complex that represses transcription of neuron-specific genes in non-neuronal cells. The BHC complex is recruited at RE1/NRSE sites by REST and acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier. In the BHC complex, it serves as a molecular beacon for the recruitment of molecular machinery, including MeCP2 and SUV39H1, that imposes silencing across a chromosomal interval. Plays a central role in demethylation of Lys-4 of histone H3 by promoting demethylase activity of KDM1A on core histones and nucleosomal substrates. It also protects KDM1A from the proteasome. 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 and controls hematopoietic differentiation.<ref>PMID:11516394</ref> <ref>PMID:11171972</ref> <ref>PMID:12032298</ref> <ref>PMID:12399542</ref> <ref>PMID:12493763</ref> <ref>PMID:16140033</ref> <ref>PMID:16079794</ref> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Ciossani, G]] | |||
[[Category: Forgione, M]] | [[Category: Forgione, M]] | ||
[[Category: | [[Category: Forneris, F]] | ||
[[Category: Lucidi, A]] | |||
[[Category: Mai, A]] | |||
[[Category: Mattevi, A]] | |||
[[Category: Pilotto, S]] | |||
[[Category: Rotili, D]] | [[Category: Rotili, D]] | ||
[[Category: Speranzini, V]] | [[Category: Speranzini, V]] | ||
[[Category: Velankar, S]] | [[Category: Velankar, S]] | ||
[[Category: Chromatin]] | |||
[[Category: Corest1]] | |||
[[Category: Epigenetic]] | |||
[[Category: Kdm1a]] | |||
[[Category: Lsd1]] | |||
[[Category: Oxidoreductase-repressor complex]] | |||