3abu

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[[Image:3abu.png|left|200px]]
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==Crystal Structure of LSD1 in complex with a 2-PCPA derivative, S1201==
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<StructureSection load='3abu' size='340' side='right' caption='[[3abu]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3abu]] is a 1 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=3ABU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ABU FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=12F:[(2R,3S,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-3,4-DIHYDROXYTETRAHYDROFURAN-2-YL]METHYL+(2R,3S,4S)-5-[(1R,3R,3AS)-3-[2-(BENZYLOXY)-3-FLUOROPHENYL]-1-HYDROXY-10,11-DIMETHYL-4,6-DIOXO-2,3,5,6-TETRAHYDRO-1H-BENZO[G]PYRROLO[2,1-E]PTERIDIN-8(4H)-YL]-2,3,4-TRIHYDROXYPENTYL+DIHYDROGEN+DIPHOSPHATE'>12F</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2dw4|2dw4]], [[2z5u|2z5u]], [[2uxx|2uxx]], [[3abt|3abt]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Kazusa DNA KIAA 0601 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<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=3abu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3abu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3abu RCSB], [http://www.ebi.ac.uk/pdbsum/3abu 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/ab/3abu_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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Lysine-specific demethylase 1 (LSD1/KDM1) demethylates histone H3, in addition to the tumor suppressor p53 and DNA methyltransferase 1 (Dnmt1), thus regulating eukaryotic gene expression by altering chromatin structure. Specific inhibitors of LSD1 are desired as anti-cancer agents, since LSD1 aberrations are associated with several cancers, and LSD1 inhibition restores the expression of abnormally silenced genes in cancerous cells. In this study, we designed and synthesized several candidate compounds to inhibit LSD1, based on the structures of LSD1 and monoamine oxidase B (MAO-B), in complex with an anti-depressant tranylcypromine (2-PCPA) derivative. The compound S2101 showed stronger LSD1 inhibition than tranylcypromine and the known small LSD1 inhibitors in LSD1 demethylation assays, with &lt;i&gt;k&lt;/i&gt;&lt;sub&gt;inact&lt;/sub&gt;/&lt;i&gt;K&lt;sub&gt;I&lt;/sub&gt;&lt;/i&gt; values of 4560 M &lt;sup&gt;-1&lt;/sup&gt; s &lt;sup&gt;-1&lt;/sup&gt;. In comparison with tranylcypromine, the compound displayed weaker inhibition of the monoamine oxidases. The inhibition modes of the two 2-PCPA derivatives, 2-PFPA and S1201, were identified by determining the inhibitor-bound LSD1 structures, which revealed the enhanced stability of the inhibitor-FAD adducts by their interactions with the surrounding LSD1 residues. These molecules are potential pharmaceutical candidates for cancer or latent virus infection, as well as research tools for LSD1-related biological investigations.&lt;i&gt;&lt;/i&gt;&lt;sub&gt;&lt;/sub&gt;&lt;sup&gt;&lt;/sup&gt;
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{{STRUCTURE_3abu| PDB=3abu | SCENE= }}
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Structurally Designed &lt;i&gt;Trans&lt;/i&gt;-2-phenylcyclopropylamine Derivatives Potently Inhibit Histone Demethylase LSD1/KDM1.,Mimasu S, Umezawa N, Sato S, Higuchi T, Umehara T, Yokoyama S Biochemistry. 2010 Jun 22. PMID:20568732<ref>PMID:20568732</ref>
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===Crystal Structure of LSD1 in complex with a 2-PCPA derivative, S1201===
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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>
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{{ABSTRACT_PUBMED_20568732}}
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== References ==
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<references/>
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==About this Structure==
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__TOC__
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[[3abu]] is a 1 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=3ABU OCA].
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</StructureSection>
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==See Also==
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*[[Lysine-specific histone demethylase 1|Lysine-specific histone demethylase 1]]
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==Reference==
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<ref group="xtra">PMID:020568732</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Higuchi, T.]]
[[Category: Higuchi, T.]]

Revision as of 12:03, 29 October 2014

Crystal Structure of LSD1 in complex with a 2-PCPA derivative, S1201

3abu, resolution 3.10Å

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