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[[Image:3btx.jpg|left|200px]]
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{{STRUCTURE_3btx|  PDB=3btx  |  SCENE=  }}
'''X-ray structure of human ABH2 bound to dsDNA through active site cross-linking'''


==X-ray structure of human ABH2 bound to dsDNA through active site cross-linking==
<StructureSection load='3btx' size='340' side='right'caption='[[3btx]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3btx]] 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=3BTX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BTX 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2YR:2-DEOXY-N-(2-SULFANYLETHYL)CYTIDINE+5-(DIHYDROGEN+PHOSPHATE)'>2YR</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=3btx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3btx OCA], [https://pdbe.org/3btx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3btx RCSB], [https://www.ebi.ac.uk/pdbsum/3btx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3btx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ALKB2_HUMAN ALKB2_HUMAN] Dioxygenase that repairs alkylated DNA and RNA containing 1-methyladenine and 3-methylcytosine by oxidative demethylation. Can also repair alkylated DNA containing 1-ethenoadenine (in vitro). Has strong preference for double-stranded DNA. Has low efficiency with single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron.<ref>PMID:12486230</ref> <ref>PMID:12594517</ref> <ref>PMID:16174769</ref> <ref>PMID:18519673</ref> <ref>PMID:18432238</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bt/3btx_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=3btx ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Escherichia coli AlkB and its human homologues ABH2 and ABH3 repair DNA/RNA base lesions by using a direct oxidative dealkylation mechanism. ABH2 has the primary role of guarding mammalian genomes against 1-meA damage by repairing this lesion in double-stranded DNA (dsDNA), whereas AlkB and ABH3 preferentially repair single-stranded DNA (ssDNA) lesions and can repair damaged bases in RNA. Here we show the first crystal structures of AlkB-dsDNA and ABH2-dsDNA complexes, stabilized by a chemical cross-linking strategy. This study reveals that AlkB uses an unprecedented base-flipping mechanism to access the damaged base: it squeezes together the two bases flanking the flipped-out one to maintain the base stack, explaining the preference of AlkB for repairing ssDNA lesions over dsDNA ones. In addition, the first crystal structure of ABH2, presented here, provides a structural basis for designing inhibitors of this human DNA repair protein.


==Overview==
Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA.,Yang CG, Yi C, Duguid EM, Sullivan CT, Jian X, Rice PA, He C Nature. 2008 Apr 24;452(7190):961-5. PMID:18432238<ref>PMID:18432238</ref>
Escherichia coli AlkB and its human homologues ABH2 and ABH3 repair DNA/RNA base lesions by using a direct oxidative dealkylation mechanism. ABH2 has the primary role of guarding mammalian genomes against 1-meA damage by repairing this lesion in double-stranded DNA (dsDNA), whereas AlkB and ABH3 preferentially repair single-stranded DNA (ssDNA) lesions and can repair damaged bases in RNA. Here we show the first crystal structures of AlkB-dsDNA and ABH2-dsDNA complexes, stabilized by a chemical cross-linking strategy. This study reveals that AlkB uses an unprecedented base-flipping mechanism to access the damaged base: it squeezes together the two bases flanking the flipped-out one to maintain the base stack, explaining the preference of AlkB for repairing ssDNA lesions over dsDNA ones. In addition, the first crystal structure of ABH2, presented here, provides a structural basis for designing inhibitors of this human DNA repair protein.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
3BTX is a [[Protein complex]] structure of sequences 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=3BTX OCA].
</div>
<div class="pdbe-citations 3btx" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA., Yang CG, Yi C, Duguid EM, Sullivan CT, Jian X, Rice PA, He C, Nature. 2008 Apr 24;452(7190):961-5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18432238 18432238]
*[[Dioxygenase 3D structures|Dioxygenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: He, C.]]
[[Category: He C]]
[[Category: Yang, C G.]]
[[Category: Yang C-G]]
[[Category: Yi, C.]]
[[Category: Yi C]]
[[Category: Cross-linking]]
[[Category: Dna damage]]
[[Category: Dna repair]]
[[Category: Human dioxygenase]]
[[Category: Iron]]
[[Category: Metal-binding]]
[[Category: Nucleus]]
[[Category: Oxidoreductase]]
[[Category: Oxidoreductase/dna complex]]
[[Category: Protein/dna interaction]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 11 10:57:23 2008''

Latest revision as of 09:43, 6 November 2024

X-ray structure of human ABH2 bound to dsDNA through active site cross-linking

3btx, resolution 2.00Å

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