4oct

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{{STRUCTURE_4oct| PDB=4oct | SCENE= }}
 
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===Crystal structure of human ALKBH5 crystallized in the presence of Mn^{2+} and 2-oxoglutarate===
 
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==Function==
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==Crystal structure of human ALKBH5 crystallized in the presence of Mn^{2+} and 2-oxoglutarate==
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[[http://www.uniprot.org/uniprot/ALKB5_HUMAN ALKB5_HUMAN]] Dioxygenase that demethylates RNA by oxidative demethylation: specifically demethylates N(6)-methyladenosine (m(6)A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes. Requires molecular oxygen, alpha-ketoglutarate and iron. Demethylation of m(6)A mRNA affects mRNA processing and export and is required for spermatogenesis.<ref>PMID:21264265</ref> <ref>PMID:23177736</ref>
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<StructureSection load='4oct' size='340' side='right'caption='[[4oct]], [[Resolution|resolution]] 2.28&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4oct]] 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=4OCT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OCT 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]] 2.28&#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=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=4oct FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oct OCA], [https://pdbe.org/4oct PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4oct RCSB], [https://www.ebi.ac.uk/pdbsum/4oct PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4oct ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/ALKB5_HUMAN ALKB5_HUMAN] Dioxygenase that demethylates RNA by oxidative demethylation: specifically demethylates N(6)-methyladenosine (m(6)A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes. Requires molecular oxygen, alpha-ketoglutarate and iron. Demethylation of m(6)A mRNA affects mRNA processing and export and is required for spermatogenesis.<ref>PMID:21264265</ref> <ref>PMID:23177736</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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N6-Methyladenosine (m6A) is the most prevalent internal RNA modification in eukaryotes. ALKBH5 belongs to the AlkB family of dioxygenases and has been shown to specifically demethylate m6A in single stranded RNA. Here we report crystal structures of ALKBH5 in the presence of either its cofactors or the ALKBH5 inhibitor citrate. Catalytic assays demonstrate that the ALKBH5 catalytic domain can demethylate both ssRNA and ssDNA. We identify the tricarboxylic acid (TCA) cycle intermediate citrate as a modest inhibitor of ALKHB5 (IC50: ~488 muM). The structural analysis reveals that a loop region of ALKBH5 is immobilized by a disulfide bond which apparently excludes the binding of dsDNA to ALKBH5. We identify the m6A binding pocket of ALKBH5 and the key residues involved in m6A recognition using mutagenesis and ITC binding experiments.
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==About this Structure==
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Structures of human ALKBH5 demethylase reveal a unique binding mode for specific single stranded m6A RNA demethylation.,Xu C, Liu K, Tempel W, Demetriades M, Aik W, Schofield CJ, Min J J Biol Chem. 2014 Apr 28. PMID:24778178<ref>PMID:24778178</ref>
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[[4oct]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OCT OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<references group="xtra"/><references/>
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</div>
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[[Category: Arrowsmith, C H.]]
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<div class="pdbe-citations 4oct" style="background-color:#fffaf0;"></div>
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[[Category: Bountra, C.]]
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[[Category: Cerovina, T.]]
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==See Also==
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[[Category: Chao, X.]]
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*[[Dioxygenase 3D structures|Dioxygenase 3D structures]]
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[[Category: Dong, A.]]
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== References ==
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[[Category: Edwards, A M.]]
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<references/>
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[[Category: He, H.]]
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__TOC__
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[[Category: Liu, K.]]
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</StructureSection>
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[[Category: Min, J.]]
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[[Category: Homo sapiens]]
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[[Category: SGC, Structural Genomics Consortium.]]
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[[Category: Large Structures]]
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[[Category: Tempel, W.]]
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[[Category: Arrowsmith CH]]
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[[Category: Oxidoreductase]]
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[[Category: Bountra C]]
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[[Category: Rna demethylase]]
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[[Category: Cerovina T]]
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[[Category: Sgc]]
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[[Category: Chao X]]
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[[Category: Structural genomic]]
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[[Category: Dong A]]
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[[Category: Structural genomics consortium]]
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[[Category: Edwards AM]]
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[[Category: He H]]
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[[Category: Liu K]]
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[[Category: Min J]]
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[[Category: Tempel W]]

Current revision

Crystal structure of human ALKBH5 crystallized in the presence of Mn^{2+} and 2-oxoglutarate

PDB ID 4oct

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