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2iuw

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[[Image:2iuw.gif|left|200px]]
 
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==Crystal structure of human ABH3 in complex with iron ion and 2- oxoglutarate==
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The line below this paragraph, containing "STRUCTURE_2iuw", creates the "Structure Box" on the page.
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<StructureSection load='2iuw' size='340' side='right'caption='[[2iuw]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2iuw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IUW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IUW FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><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=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene></td></tr>
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-->
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=LED:(4R)-5-OXO-L-LEUCINE'>LED</scene></td></tr>
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{{STRUCTURE_2iuw| PDB=2iuw | SCENE= }}
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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=2iuw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2iuw OCA], [https://pdbe.org/2iuw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2iuw RCSB], [https://www.ebi.ac.uk/pdbsum/2iuw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2iuw ProSAT]</span></td></tr>
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</table>
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'''CRYSTAL STRUCTURE OF HUMAN ABH3 IN COMPLEX WITH IRON ION AND 2-OXOGLUTARATE'''
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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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==Overview==
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/iu/2iuw_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=2iuw 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 ==
Methylating agents are ubiquitous in the environment, and central in cancer therapy. The 1-methyladenine and 3-methylcytosine lesions in DNA/RNA contribute to the cytotoxicity of such agents. These lesions are directly reversed by ABH3 (hABH3) in humans and AlkB in Escherichia coli. Here, we report the structure of the hABH3 catalytic core in complex with iron and 2-oxoglutarate (2OG) at 1.5 A resolution and analyse key site-directed mutants. The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif. This experimentally establishes hABH3 as a structural member of the Fe(II)/2OG-dependent dioxygenase superfamily, which couples substrate oxidation to conversion of 2OG into succinate and CO2. A positively charged DNA/RNA binding groove indicates a distinct nucleic acid binding conformation different from that predicted in the AlkB structure with three nucleotides. These results uncover previously unassigned key catalytic residues, identify a flexible hairpin involved in nucleotide flipping and ss/ds-DNA discrimination, and reveal self-hydroxylation of an active site leucine that may protect against uncoupled generation of dangerous oxygen radicals.
Methylating agents are ubiquitous in the environment, and central in cancer therapy. The 1-methyladenine and 3-methylcytosine lesions in DNA/RNA contribute to the cytotoxicity of such agents. These lesions are directly reversed by ABH3 (hABH3) in humans and AlkB in Escherichia coli. Here, we report the structure of the hABH3 catalytic core in complex with iron and 2-oxoglutarate (2OG) at 1.5 A resolution and analyse key site-directed mutants. The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif. This experimentally establishes hABH3 as a structural member of the Fe(II)/2OG-dependent dioxygenase superfamily, which couples substrate oxidation to conversion of 2OG into succinate and CO2. A positively charged DNA/RNA binding groove indicates a distinct nucleic acid binding conformation different from that predicted in the AlkB structure with three nucleotides. These results uncover previously unassigned key catalytic residues, identify a flexible hairpin involved in nucleotide flipping and ss/ds-DNA discrimination, and reveal self-hydroxylation of an active site leucine that may protect against uncoupled generation of dangerous oxygen radicals.
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==About this Structure==
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Human ABH3 structure and key residues for oxidative demethylation to reverse DNA/RNA damage.,Sundheim O, Vagbo CB, Bjoras M, Sousa MM, Talstad V, Aas PA, Drablos F, Krokan HE, Tainer JA, Slupphaug G EMBO J. 2006 Jul 26;25(14):3389-97. Epub 2006 Jul 6. PMID:16858410<ref>PMID:16858410</ref>
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2IUW is a [[Single protein]] structure of 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=2IUW 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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Human ABH3 structure and key residues for oxidative demethylation to reverse DNA/RNA damage., Sundheim O, Vagbo CB, Bjoras M, Sousa MM, Talstad V, Aas PA, Drablos F, Krokan HE, Tainer JA, Slupphaug G, EMBO J. 2006 Jul 26;25(14):3389-97. Epub 2006 Jul 6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16858410 16858410]
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</div>
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[[Category: Homo sapiens]]
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<div class="pdbe-citations 2iuw" style="background-color:#fffaf0;"></div>
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[[Category: Single protein]]
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== References ==
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[[Category: Aas, P A.]]
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<references/>
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[[Category: Bjoras, M.]]
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__TOC__
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[[Category: Desousa, M M.L.]]
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</StructureSection>
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[[Category: Drablos, F.]]
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[[Category: Human]]
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[[Category: Krokan, H E.]]
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[[Category: Large Structures]]
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[[Category: Slupphaug, G.]]
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[[Category: Aas, P A]]
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[[Category: Sundheim, O.]]
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[[Category: Bjoras, M]]
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[[Category: Tainer, J A.]]
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[[Category: Drablos, F]]
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[[Category: Talstad, V.]]
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[[Category: Krokan, H E]]
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[[Category: Vagbo, C B.]]
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[[Category: Slupphaug, G]]
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[[Category: Sundheim, O]]
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[[Category: Tainer, J A]]
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[[Category: Talstad, V]]
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[[Category: Vagbo, C B]]
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[[Category: DeSousa, M M.L]]
[[Category: Beta jellyroll]]
[[Category: Beta jellyroll]]
[[Category: Demethylase]]
[[Category: Demethylase]]
[[Category: Dna/rna repair]]
[[Category: Dna/rna repair]]
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[[Category: Fe/2og-dependent dioxygenase]]
 
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[[Category: Mad]]
 
[[Category: Oxidoreductase]]
[[Category: Oxidoreductase]]
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[[Category: Polymorphism]]
 
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 07:54:53 2008''
 

Current revision

Crystal structure of human ABH3 in complex with iron ion and 2- oxoglutarate

PDB ID 2iuw

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