OCA at 17:30, 29 November 2023

OCA — Wed, 29 Nov 2023 17:30:42 GMT

←Older revision		Revision as of 17:30, 29 November 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 7vqs is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of LSD1 in complex with compound 4==
		+	<StructureSection load='7vqs' size='340' side='right'caption='[[7vqs]], [[Resolution\|resolution]] 2.94Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7vqs]] 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=7VQS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VQS 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]] 2.94Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7UQ:3-[3,5-bis(fluoranyl)-2-[(2-fluoranylpyridin-3-yl)methoxy]phenyl]propanal'>7UQ</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</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=7vqs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vqs OCA], [https://pdbe.org/7vqs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vqs RCSB], [https://www.ebi.ac.uk/pdbsum/7vqs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vqs 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Lysine-specific demethylase 1 (LSD1/KDM1A) is a promising therapeutic target for the treatment of cancers. Several derivatives of tranylcypromine (trans-2-phenylcyclopropylamine) have been developed as LSD1 inhibitors. One such derivative is S2157; however, this compound has a high hERG channel inhibitory activity and a low microsomal stability, making it unsuitable as a drug candidate. Here, using an in silico hERG inhibition prediction model, we designed, synthesized, and evaluated a novel series of S2157 derivatives characterized by modifications of the benzyloxy and piperazine groups. Among the synthesized derivatives, a compound possessing 2-fluoropyridine and 2,8-diaza-spiro[4.5]decane groups (compound 10) showed the most desirable activities, and its eutomer, S1427, was isolated by the optical resolution of 10. In addition to potent LSD1 inhibitory activity, S1427 exhibited desirable hERG channel inhibition and microsomal stability profiles.

-	~~Authors~~:	+	Design and Synthesis of Tranylcypromine-Derived LSD1 Inhibitors with Improved hERG and Microsomal Stability Profiles.,Koda Y, Sato S, Yamamoto H, Niwa H, Watanabe H, Watanabe C, Sato T, Nakamura K, Tanaka A, Shirouzu M, Honma T, Fukami T, Koyama H, Umehara T ACS Med Chem Lett. 2022 Apr 29;13(5):848-854. doi: , 10.1021/acsmedchemlett.2c00120. eCollection 2022 May 12. PMID:35586426<ref>PMID:35586426</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 7vqs" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Lysine-specific histone demethylase 3D structures\|Lysine-specific histone demethylase 3D structures]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Koda Y]]
		+	[[Category: Koyama H]]
		+	[[Category: Niwa H]]
		+	[[Category: Sato S]]
		+	[[Category: Umehara T]]
		+	[[Category: Yamamoto H]]

OCA at 12:18, 17 November 2021

OCA — Wed, 17 Nov 2021 12:18:41 GMT

←Older revision		Revision as of 12:18, 17 November 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7vqs is ON HOLD	+	The entry 7vqs is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7vqs" [edit=sysop:move=sysop]

OCA — Wed, 27 Oct 2021 12:53:27 GMT

Protected "7vqs" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:53, 27 October 2021

OCA: New page: '''Unreleased structure''' The entry 7vqs is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 27 Oct 2021 12:53:26 GMT

New page: '''Unreleased structure''' The entry 7vqs is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7vqs is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7vqs - Revision history

OCA at 17:30, 29 November 2023

OCA at 12:18, 17 November 2021

OCA: Protected "7vqs" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7vqs is ON HOLD Authors: Description: Category: Unreleased Structures