2uxx

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{{STRUCTURE_2uxx| PDB=2uxx | SCENE= }}
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==Human LSD1 Histone Demethylase-CoREST in complex with an FAD- tranylcypromine adduct==
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===Human LSD1 Histone Demethylase-CoREST in complex with an FAD- tranylcypromine adduct===
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<StructureSection load='2uxx' size='340' side='right' caption='[[2uxx]], [[Resolution|resolution]] 2.74&Aring;' scene=''>
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{{ABSTRACT_PUBMED_17569509}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2uxx]] is a 2 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=2UXX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2UXX FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FAJ:FAD-TRANS-2-PHENYLCYCLOPROPYLAMINE+ADDUCT'>FAJ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene><br>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2com|2com]], [[2h94|2h94]], [[2iw5|2iw5]], [[2uxn|2uxn]]</td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2uxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uxx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2uxx RCSB], [http://www.ebi.ac.uk/pdbsum/2uxx PDBsum]</span></td></tr>
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<table>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ux/2uxx_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Histone modifications, such as acetylation and methylation, are important epigenetic marks that regulate diverse biological processes that use chromatin as the template, including transcription. Dysregulation of histone acetylation and methylation leads to the silencing of tumor suppressor genes and contributes to cancer progression. Inhibitors of enzymes that catalyze the addition and removal of these epigenetic marks thus have therapeutic potential for treating cancer. Lysine-specific demethylase 1 (LSD1) is the first discovered histone lysine demethylase and, with the help of its cofactor CoREST, specifically demethylates mono- and dimethylated histone H3 lysine 4 (H3-K4), thus repressing transcription. Because LSD1 belongs to the family of flavin adenine dinucleotide (FAD)-dependent amine oxidases, certain inhibitors of monoamine oxidases (MAOs), including the clinically used antidepressant trans-2-phenylcyclopropylamine (PCPA; tranylcypromine; Parnate), are also capable of inhibiting LSD1. In this study, we have further measured the kinetic parameters of the inhibition of LSD1 by PCPA and determined the crystal structure of LSD1-CoREST in the presence of PCPA. Our structural and mass spectrometry analyses are consistent with PCPA forming a covalent adduct with FAD in LSD1 that is distinct from the FAD-PCPA adduct of MAO B. The structure also reveals that the phenyl ring of the FAD-PCPA adduct in LSD1 does not form extensive interactions with active-site residues. This study thus provides the basis for designing more potent inhibitors of LSD1 that contain substitutions on the phenyl ring of PCPA to fully engage neighboring residues.
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==About this Structure==
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Structural basis for the inhibition of the LSD1 histone demethylase by the antidepressant trans-2-phenylcyclopropylamine.,Yang M, Culhane JC, Szewczuk LM, Jalili P, Ball HL, Machius M, Cole PA, Yu H Biochemistry. 2007 Jul 10;46(27):8058-65. Epub 2007 Jun 15. PMID:17569509<ref>PMID:17569509</ref>
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[[2uxx]] is a 2 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=2UXX OCA].
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
==See Also==
==See Also==
*[[Lysine-specific histone demethylase 1|Lysine-specific histone demethylase 1]]
*[[Lysine-specific histone demethylase 1|Lysine-specific histone demethylase 1]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:017569509</ref><ref group="xtra">PMID:016885027</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Cole, P A.]]
[[Category: Cole, P A.]]

Revision as of 01:24, 1 October 2014

Human LSD1 Histone Demethylase-CoREST in complex with an FAD- tranylcypromine adduct

2uxx, resolution 2.74Å

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