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[[Image:2fd8.gif|left|200px]]


{{Structure
==Crystal Structure of AlkB in complex with Fe(II), 2-oxoglutarate, and methylated trinucleotide T-meA-T==
|PDB= 2fd8 |SIZE=350|CAPTION= <scene name='initialview01'>2fd8</scene>, resolution 2.300&Aring;
<StructureSection load='2fd8' size='340' side='right'caption='[[2fd8]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene> and <scene name='pdbligand=AKG:2-OXYGLUTARIC ACID'>AKG</scene>
<table><tr><td colspan='2'>[[2fd8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FD8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FD8 FirstGlance]. <br>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
|GENE= alkB, aidD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])
<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=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=MA7:1N-METHYLADENOSINE-5-MONOPHOSPHATE'>MA7</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=2fd8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fd8 OCA], [https://pdbe.org/2fd8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fd8 RCSB], [https://www.ebi.ac.uk/pdbsum/2fd8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fd8 ProSAT], [https://www.topsan.org/Proteins/NESGC/2fd8 TOPSAN]</span></td></tr>
</table>
== Function ==
[https://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/fd/2fd8_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=2fd8 ConSurf].
<div style="clear:both"></div>


'''Crystal Structure of AlkB in complex with Fe(II), 2-oxoglutarate, and methylated trinucleotide T-meA-T'''
==See Also==
 
*[[Dioxygenase 3D structures|Dioxygenase 3D structures]]
 
== References ==
==Overview==
<references/>
Nucleic acid damage by environmental and endogenous alkylation reagents creates lesions that are both mutagenic and cytotoxic, with the latter effect accounting for their widespread use in clinical cancer chemotherapy. Escherichia coli AlkB and the homologous human proteins ABH2 and ABH3 (refs 5, 7) promiscuously repair DNA and RNA bases damaged by S(N)2 alkylation reagents, which attach hydrocarbons to endocyclic ring nitrogen atoms (N1 of adenine and guanine and N3 of thymine and cytosine). Although the role of AlkB in DNA repair has long been established based on phenotypic studies, its exact biochemical activity was only elucidated recently after sequence profile analysis revealed it to be a member of the Fe-oxoglutarate-dependent dioxygenase superfamily. These enzymes use an Fe(II) cofactor and 2-oxoglutarate co-substrate to oxidize organic substrates. AlkB hydroxylates an alkylated nucleotide base to produce an unstable product that releases an aldehyde to regenerate the unmodified base. Here we have determined crystal structures of substrate and product complexes of E. coli AlkB at resolutions from 1.8 to 2.3 A. Whereas the Fe-2-oxoglutarate dioxygenase core matches that in other superfamily members, a unique subdomain holds a methylated trinucleotide substrate into the active site through contacts to the polynucleotide backbone. Amide hydrogen exchange studies and crystallographic analyses suggest that this substrate-binding 'lid' is conformationally flexible, which may enable docking of diverse alkylated nucleotide substrates in optimal catalytic geometry. Different crystal structures show open and closed states of a tunnel putatively gating O2 diffusion into the active site. Exposing crystals of the anaerobic Michaelis complex to air yields slow but substantial oxidation of 2-oxoglutarate that is inefficiently coupled to nucleotide oxidation. These observations suggest that protein dynamics modulate redox chemistry and that a hypothesized migration of the reactive oxy-ferryl ligand on the catalytic Fe ion may be impeded when the protein is constrained in the crystal lattice.
__TOC__
 
</StructureSection>
==About this Structure==
[[Category: Escherichia coli K-12]]
2FD8 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FD8 OCA].
[[Category: Large Structures]]
 
[[Category: Benach J]]
==Reference==
[[Category: Edstrom WC]]
Crystal structures of catalytic complexes of the oxidative DNA/RNA repair enzyme AlkB., Yu B, Edstrom WC, Benach J, Hamuro Y, Weber PC, Gibney BR, Hunt JF, Nature. 2006 Feb 16;439(7078):879-84. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16482161 16482161]
[[Category: Gibney BR]]
[[Category: Escherichia coli]]
[[Category: Hunt JF]]
[[Category: Single protein]]
[[Category: Yu B]]
[[Category: Benach, J.]]
[[Category: Edstrom, W C.]]
[[Category: Gibney, B R.]]
[[Category: Hunt, J F.]]
[[Category: NESG, Northeast Structural Genomics Consortium.]]
[[Category: Yu, B.]]
[[Category: AKG]]
[[Category: FE2]]
[[Category: beta jellyroll]]
[[Category: nesg]]
[[Category: northeast structural genomics consortium]]
[[Category: protein structure initiative]]
[[Category: psi]]
[[Category: structural genomic]]
 
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Retrieved from "https://proteopedia.org/2fd8"