3zms

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{{STRUCTURE_3zms| PDB=3zms | SCENE= }}
 
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===LSD1-CoREST in complex with INSM1 peptide===
 
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{{ABSTRACT_PUBMED_23721412}}
 
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==Disease==
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==LSD1-CoREST in complex with INSM1 peptide==
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[[http://www.uniprot.org/uniprot/INSM1_HUMAN INSM1_HUMAN]] Endocrine tumor.
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<StructureSection load='3zms' size='340' side='right'caption='[[3zms]], [[Resolution|resolution]] 2.96&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3zms]] 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=3ZMS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZMS FirstGlance]. <br>
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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]] 2.96&#8491;</td></tr>
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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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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3zms FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zms OCA], [https://pdbe.org/3zms PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zms RCSB], [https://www.ebi.ac.uk/pdbsum/3zms PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zms 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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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The combinatorial assembly of protein complexes is at the heart of chromatin biology. Lysine demethylase LSD1(KDM1A)/CoREST beautifully exemplifies this concept. The active site of the enzyme tightly associates to the N-terminal domain of transcription factors of the SNAIL1 family, which therefore can competitively inhibit the binding of the N-terminal tail of the histone substrate. Our enzymatic, crystallographic, spectroscopic, and computational studies reveal that LSD1/CoREST can bind to a hexapeptide derived from the SNAIL sequence through recognition of a positively charged alpha-helical turn that forms upon binding to the enzyme. Variations in sequence and length of this six amino acid ligand modulate affinities enabling the same binding site to differentially interact with proteins that exert distinct biological functions. The discovered short peptide inhibitors exhibit antiproliferative activities and lay the foundation for the development of peptidomimetic small molecule inhibitors of LSD1.
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==Function==
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PROTEIN RECOGNITION BY SMALL PEPTIDE REVERSIBLE INHIBITORS OF THE CHROMATIN-MODIFYING LSD1/CoREST LYSINE DEMETHYLASE.,Tortorici M, Borrello MT, Tardugno M, Chiarelli LR, Pilotto S, Ciossani G, Vellore NA, Bailey SG, Cowan J, O'Connell M, Crabb SJ, Packham GK, Mai A, Baron R, Ganesan A, Mattevi A ACS Chem Biol. 2013 May 30. PMID:23721412<ref>PMID:23721412</ref>
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[[http://www.uniprot.org/uniprot/INSM1_HUMAN INSM1_HUMAN]] May be associated with the transformation of neuroendocrine cells. [[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>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3zms]] is a 3 chain structure 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=3ZMS OCA].
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</div>
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<div class="pdbe-citations 3zms" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
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*[[Lysine-specific histone demethylase 1|Lysine-specific histone demethylase 1]]
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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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==Reference==
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<references/>
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<ref group="xtra">PMID:023721412</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Baron, R.]]
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[[Category: Large Structures]]
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[[Category: Borrello, M T.]]
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[[Category: Baron R]]
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[[Category: Chiarelli, L R.]]
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[[Category: Borrello MT]]
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[[Category: Ciossani, G.]]
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[[Category: Chiarelli LR]]
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[[Category: Connell, M O.]]
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[[Category: Ciossani G]]
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[[Category: Cowan, J.]]
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[[Category: Cowan J]]
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[[Category: Ganesan, A.]]
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[[Category: Ganesan A]]
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[[Category: Mai, A.]]
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[[Category: Mai A]]
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[[Category: Mattevi, A.]]
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[[Category: Mattevi A]]
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[[Category: Pilotto, S.]]
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[[Category: O'Connell M]]
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[[Category: Tardugno, M.]]
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[[Category: Pilotto S]]
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[[Category: Tortorici, M.]]
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[[Category: Tardugno M]]
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[[Category: Vellore, N A.]]
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[[Category: Tortorici M]]
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[[Category: Chromatin]]
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[[Category: Vellore NA]]
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[[Category: Demethylase]]
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[[Category: Oxidoreductase-peptide complex]]
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[[Category: Transcription factor]]
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Current revision

LSD1-CoREST in complex with INSM1 peptide

PDB ID 3zms

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