View source for 4gus


==Crystal structure of LSD2-NPAC with H3 in space group P3221==
<StructureSection load='4gus' size='340' side='right'caption='[[4gus]], [[Resolution|resolution]] 2.23&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4gus]] 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=4GUS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GUS 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]] 2.23&#8491;</td></tr>
<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>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4gus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gus OCA], [https://pdbe.org/4gus PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gus RCSB], [https://www.ebi.ac.uk/pdbsum/4gus PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gus ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/KDM1B_HUMAN KDM1B_HUMAN] Histone demethylase that demethylates 'Lys-4' of histone H3, a specific tag for epigenetic transcriptional activation, thereby acting as a corepressor. Required for de novo DNA methylation of a subset of imprinted genes during oogenesis. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Demethylates both mono- and di-methylated 'Lys-4' of histone H3. Has no effect on tri-methylated 'Lys-4', mono-, di- or tri-methylated 'Lys-9', mono-, di- or tri-methylated 'Lys-27', mono-, di- or tri-methylated 'Lys-36' of histone H3, or on mono-, di- or tri-methylated 'Lys-20' of histone H4 (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Dynamic regulation of histone methylation represents a fundamental epigenetic mechanism underlying eukaryotic gene regulation, yet little is known about how the catalytic activities of histone demethylases are regulated. Here, we identify and characterize NPAC/GLYR1 as an LSD2/KDM1b-specific cofactor that stimulates H3K4me1 and H3K4me2 demethylation. We determine the crystal structures of LSD2 alone and LSD2 in complex with the NPAC linker region in the absence or presence of histone H3 peptide, at resolutions of 2.9, 2.0, and 2.25 A, respectively. These crystal structures and further biochemical characterization define a dodecapeptide of NPAC (residues 214-225) as the minimal functional unit for its cofactor activity and provide structural determinants and a molecular mechanism underlying the intrinsic cofactor activity of NPAC in stimulating LSD2-catalyzed H3K4 demethylation. Thus, these findings establish a model for how a cofactor directly regulates histone demethylation and will have a significant impact on our understanding of catalytic-activity-based epigenetic regulation.

LSD2/KDM1B and Its Cofactor NPAC/GLYR1 Endow a Structural and Molecular Model for Regulation of H3K4 Demethylation.,Fang R, Chen F, Dong Z, Hu D, Barbera AJ, Clark EA, Fang J, Yang Y, Mei P, Rutenberg M, Li Z, Zhang Y, Xu Y, Yang H, Wang P, Simon MD, Zhou Q, Li J, Marynick MP, Li X, Lu H, Kaiser UB, Kingston RE, Xu Y, Shi YG Mol Cell. 2012 Dec 19. pii: S1097-2765(12)00976-8. doi:, 10.1016/j.molcel.2012.11.019. PMID:23260659<ref>PMID:23260659</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4gus" 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: Chen F]]
[[Category: Dong Z]]
[[Category: Fang J]]
[[Category: Fang R]]
[[Category: Li Z]]
[[Category: Shi Y]]
[[Category: Wang P]]
[[Category: Xu Y]]
[[Category: Yang H]]
[[Category: Yang Y]]