2wwu

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{{STRUCTURE_2wwu| PDB=2wwu | SCENE= }}
 
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===Crystal structure of the catalytic domain of PHD finger protein 8===
 
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{{ABSTRACT_PUBMED_20067792}}
 
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==Disease==
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==Crystal structure of the catalytic domain of PHD finger protein 8==
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[[http://www.uniprot.org/uniprot/PHF8_HUMAN PHF8_HUMAN]] Defects in PHF8 are the cause of mental retardation syndromic X-linked Siderius type (MRXSSD) [MIM:[http://omim.org/entry/300263 300263]]. A disorder characterized by mild to borderline mental retardation with or without cleft lip/cleft palate.<ref>PMID:20548336</ref><ref>PMID:20346720</ref><ref>PMID:20421419</ref><ref>PMID:20208542</ref><ref>PMID:20622853</ref><ref>PMID:20622854</ref><ref>PMID:20101266</ref><ref>PMID:16199551</ref><ref>PMID:17661819</ref>
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<StructureSection load='2wwu' size='340' side='right'caption='[[2wwu]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2wwu]] 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=2WWU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WWU FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2wwu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wwu OCA], [https://pdbe.org/2wwu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wwu RCSB], [https://www.ebi.ac.uk/pdbsum/2wwu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wwu ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/PHF8_HUMAN PHF8_HUMAN] Defects in PHF8 are the cause of mental retardation syndromic X-linked Siderius type (MRXSSD) [MIM:[https://omim.org/entry/300263 300263]. A disorder characterized by mild to borderline mental retardation with or without cleft lip/cleft palate.<ref>PMID:20548336</ref> <ref>PMID:20346720</ref> <ref>PMID:20421419</ref> <ref>PMID:20208542</ref> <ref>PMID:20622853</ref> <ref>PMID:20622854</ref> <ref>PMID:20101266</ref> <ref>PMID:16199551</ref> <ref>PMID:17661819</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/PHF8_HUMAN PHF8_HUMAN] Histone lysine demethylase with selectivity for the di- and monomethyl states that plays a key role cell cycle progression, rDNA transcription and brain development. Demethylates mono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2), dimethylated H3 'Lys-27' (H3K27Me2) and monomethylated histone H4 'Lys-20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks. Involved in cell cycle progression by being required to control G1-S transition. Acts as a coactivator of rDNA transcription, by activating polymerase I (pol I) mediated transcription of rRNA genes. Required for brain development, probably by regulating expression of neuron-specific genes. Only has activity toward H4K20Me1 when nucleosome is used as a substrate and when not histone octamer is used as substrate. May also have weak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however, the relevance of this result remains unsure in vivo. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: has weak activity toward H3K9Me2 in absence of H3K4me3, while it has high activity toward H3K9me2 when binding H3K4me3.<ref>PMID:20531378</ref> <ref>PMID:20548336</ref> <ref>PMID:19843542</ref> <ref>PMID:20346720</ref> <ref>PMID:20421419</ref> <ref>PMID:20208542</ref> <ref>PMID:20622853</ref> <ref>PMID:20622854</ref> <ref>PMID:20101266</ref> <ref>PMID:20023638</ref>
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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/ww/2wwu_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/main_output.php?pdb_ID=2wwu 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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Crystallographic analysis of the catalytic domain of PHD finger protein 8 (PHF8), an N(epsilon)-methyl lysine histone demethylase associated with mental retardation and cleft lip/palate, reveals a double-stranded beta-helix fold with conserved Fe(II) and cosubstrate binding sites typical of the 2-oxoglutarate dependent oxygenases. The PHF8 active site is highly conserved with those of the FBXL10/11demethylases, which are also selective for the di-/mono-methylated lysine states, but differs from that of the JMJD2 demethylases which are selective for tri-/di-methylated states. The results rationalize the lack of activity for the clinically observed F279S PHF8 variant and they will help to identify inhibitors selective for specific N(epsilon)-methyl lysine demethylase subfamilies.
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==Function==
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Crystal structure of the PHF8 Jumonji domain, an Nepsilon-methyl lysine demethylase.,Yue WW, Hozjan V, Ge W, Loenarz C, Cooper CD, Schofield CJ, Kavanagh KL, Oppermann U, McDonough MA FEBS Lett. 2010 Feb 19;584(4):825-30. Epub 2010 Jan 12. PMID:20067792<ref>PMID:20067792</ref>
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[[http://www.uniprot.org/uniprot/PHF8_HUMAN PHF8_HUMAN]] Histone lysine demethylase with selectivity for the di- and monomethyl states that plays a key role cell cycle progression, rDNA transcription and brain development. Demethylates mono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2), dimethylated H3 'Lys-27' (H3K27Me2) and monomethylated histone H4 'Lys-20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks. Involved in cell cycle progression by being required to control G1-S transition. Acts as a coactivator of rDNA transcription, by activating polymerase I (pol I) mediated transcription of rRNA genes. Required for brain development, probably by regulating expression of neuron-specific genes. Only has activity toward H4K20Me1 when nucleosome is used as a substrate and when not histone octamer is used as substrate. May also have weak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however, the relevance of this result remains unsure in vivo. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: has weak activity toward H3K9Me2 in absence of H3K4me3, while it has high activity toward H3K9me2 when binding H3K4me3.<ref>PMID:20531378</ref><ref>PMID:20548336</ref><ref>PMID:19843542</ref><ref>PMID:20346720</ref><ref>PMID:20421419</ref><ref>PMID:20208542</ref><ref>PMID:20622853</ref><ref>PMID:20622854</ref><ref>PMID:20101266</ref><ref>PMID:20023638</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[2wwu]] 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=2WWU OCA].
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</div>
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<div class="pdbe-citations 2wwu" style="background-color:#fffaf0;"></div>
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==Reference==
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== References ==
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<ref group="xtra">PMID:020067792</ref><references group="xtra"/><references/>
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Allerston, C.]]
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[[Category: Large Structures]]
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[[Category: Arrowsmith, C.]]
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[[Category: Allerston C]]
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[[Category: Bountra, C.]]
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[[Category: Arrowsmith C]]
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[[Category: Cooper, C.]]
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[[Category: Bountra C]]
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[[Category: Delft, F Von.]]
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[[Category: Cooper C]]
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[[Category: Edwards, A.]]
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[[Category: Edwards A]]
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[[Category: Hozjan, V.]]
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[[Category: Hozjan V]]
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[[Category: Kavanagh, K L.]]
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[[Category: Kavanagh KL]]
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[[Category: Krojer, T.]]
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[[Category: Krojer T]]
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[[Category: Mcdonough, M A.]]
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[[Category: McDonough MA]]
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[[Category: Muniz, J.]]
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[[Category: Muniz J]]
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[[Category: Oppermann, U.]]
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[[Category: Oppermann U]]
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[[Category: Salah, E.]]
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[[Category: Salah E]]
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[[Category: Schofield, C J.]]
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[[Category: Schofield CJ]]
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[[Category: Tumber, A.]]
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[[Category: Tumber A]]
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[[Category: Weigelt, J.]]
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[[Category: Weigelt J]]
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[[Category: Yue, W W.]]
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[[Category: Yue WW]]
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[[Category: Epigenetic]]
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[[Category: Von Delft F]]
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[[Category: Histone demethylase]]
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[[Category: Jmjc domain]]
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[[Category: Metal-binding protein]]
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Current revision

Crystal structure of the catalytic domain of PHD finger protein 8

PDB ID 2wwu

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