View source for 3bi3


==X-ray structure of AlkB protein bound to dsDNA containing 1meA/A with cofactors==
<StructureSection load='3bi3' size='340' side='right' caption='[[3bi3]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3bi3]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BI3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BI3 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=2YR:2-DEOXY-N-(2-SULFANYLETHYL)CYTIDINE+5-(DIHYDROGEN+PHOSPHATE)'>2YR</scene>, <scene name='pdbligand=MA7:1N-METHYLADENOSINE-5-MONOPHOSPHATE'>MA7</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2fd8|2fd8]], [[2bhz|2bhz]], [[2iuw|2iuw]], [[3bhz|3bhz]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">alkB, aidD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bi3 OCA], [http://pdbe.org/3bi3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3bi3 RCSB], [http://www.ebi.ac.uk/pdbsum/3bi3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3bi3 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/ALKB_ECOLI ALKB_ECOLI]] Dioxygenase that repairs alkylated DNA and RNA containing 3-methylcytosine or 1-methyladenine by oxidative demethylation. Has highest activity towards 3-methylcytosine. Has lower activity towards alkylated DNA containing ethenoadenine, and no detectable activity towards 1-methylguanine or 3-methylthymine. Accepts double-stranded and single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron. Provides extensive resistance to alkylating agents such as MMS and DMS (SN2 agents), but not to MMNG and MNU (SN1 agents).<ref>PMID:12226668</ref> <ref>PMID:12594517</ref> <ref>PMID:16482161</ref> <ref>PMID:19706517</ref> <ref>PMID:21068844</ref> <ref>PMID:20084272</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/bi/3bi3_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=3bi3 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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3bi3" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dioxygenase|Dioxygenase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Ecoli]]
[[Category: Yang, C G]]
[[Category: Yi, C]]
[[Category: Alkylation repair]]
[[Category: Dioxygenase]]
[[Category: Dna damage]]
[[Category: Dna repair]]
[[Category: Iron]]
[[Category: Metal-binding]]
[[Category: Oxidoreductase]]
[[Category: Oxidoreductase-dna complex]]
[[Category: Protein dna interaction]]