View source for 4fwf


==Complex structure of LSD2/AOF1/KDM1b with H3K4 mimic==
<StructureSection load='4fwf' size='340' side='right'caption='[[4fwf]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4fwf]] is a 2 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=4FWF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FWF 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]] 2.7&#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=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=4fwf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fwf OCA], [https://pdbe.org/4fwf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fwf RCSB], [https://www.ebi.ac.uk/pdbsum/4fwf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fwf 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 ==
LSD2/AOF1/KDM1b catalyzes demethylation of mono- and di-methylated H3K4 and plays an important role in transcriptional regulation and genomic imprinting. Here, we report the high-resolution crystal structures of apo-LSD2 and LSD2 in complex with a peptide that mimics H3K4me2. Three structural domains of LSD2, namely, the novel N-terminal zinc finger, the centrally located SWIRM domain, and the C-terminal oxidase domain, closely pack together to form a boot-shaped structure. The active site cavity in the oxidase domain is large enough to accommodate several residues of the histone H3 tail and cannot discriminate between the different states of H3K4 methylation. The N-terminal zinc-finger domain, composed of a novel C4H2C2-type zinc finger and a specific CW-type zinc finger, is required for demethylase activity and, surprisingly, the binding of cofactor flavin adenine dinucleotide (FAD). In fact, a relay of extensive interactions through the zinc finger-SWIRM-oxidase domains is required for LSD2 demethylase activity and the binding of FAD. These results reveal a novel mechanism for the zinc finger and SWIRM domains in controlling LSD2 demethylase activity and provide a framework for elucidating the regulation and function of LSD2.Cell Research advance online publication 25 December 2012; doi:10.1038/cr.2012.177.

Structure-function analysis reveals a novel mechanism for regulation of histone demethylase LSD2/AOF1/KDM1b.,Zhang Q, Qi S, Xu M, Yu L, Tao Y, Deng Z, Wu W, Li J, Chen Z, Wong J Cell Res. 2012 Dec 25. doi: 10.1038/cr.2012.177. PMID:23266887<ref>PMID:23266887</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4fwf" 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 Z]]
[[Category: Zhang Q]]