3bi3: Difference between revisions

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==X-ray structure of AlkB protein bound to dsDNA containing 1meA/A with cofactors==
==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=''>
<StructureSection load='3bi3' size='340' side='right'caption='[[3bi3]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
== 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>
<table><tr><td colspan='2'>[[3bi3]] is a 3 chain structure with sequence from [https://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 [https://proteopedia.org/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>
</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=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='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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2fd8|2fd8]], [[2bhz|2bhz]], [[2iuw|2iuw]], [[3bhz|3bhz]]</div></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">alkB, aidD ([https://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>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bi3 OCA], [https://pdbe.org/3bi3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bi3 RCSB], [https://www.ebi.ac.uk/pdbsum/3bi3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bi3 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== 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>   
[[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 ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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==See Also==
==See Also==
*[[Dioxygenase|Dioxygenase]]
*[[Dioxygenase 3D structures|Dioxygenase 3D structures]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Ecoli]]
[[Category: Ecoli]]
[[Category: Large Structures]]
[[Category: Yang, C G]]
[[Category: Yang, C G]]
[[Category: Yi, C]]
[[Category: Yi, C]]

Revision as of 21:57, 20 October 2021

X-ray structure of AlkB protein bound to dsDNA containing 1meA/A with cofactorsX-ray structure of AlkB protein bound to dsDNA containing 1meA/A with cofactors

Structural highlights

3bi3 is a 3 chain structure with sequence from Ecoli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:,
NonStd Res:,
Gene:alkB, aidD (ECOLI)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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).[1] [2] [3] [4] [5] [6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Falnes PO, Johansen RF, Seeberg E. AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli. Nature. 2002 Sep 12;419(6903):178-82. PMID:12226668 doi:10.1038/nature01048
  2. ↑ Aas PA, Otterlei M, Falnes PO, Vagbo CB, Skorpen F, Akbari M, Sundheim O, Bjoras M, Slupphaug G, Seeberg E, Krokan HE. Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA. Nature. 2003 Feb 20;421(6925):859-63. PMID:12594517 doi:10.1038/nature01363
  3. ↑ Yu B, Edstrom WC, Benach J, Hamuro Y, Weber PC, Gibney BR, Hunt JF. Crystal structures of catalytic complexes of the oxidative DNA/RNA repair enzyme AlkB. Nature. 2006 Feb 16;439(7078):879-84. PMID:16482161 doi:10.1038/nature04561
  4. ↑ Yu B, Hunt JF. Enzymological and structural studies of the mechanism of promiscuous substrate recognition by the oxidative DNA repair enzyme AlkB. Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14315-20. Epub 2009 Aug 11. PMID:19706517
  5. ↑ Yi C, Jia G, Hou G, Dai Q, Zhang W, Zheng G, Jian X, Yang CG, Cui Q, He C. Iron-catalysed oxidation intermediates captured in a DNA repair dioxygenase. Nature. 2010 Nov 11;468(7321):330-3. PMID:21068844 doi:10.1038/nature09497
  6. ↑ Holland PJ, Hollis T. Structural and mutational analysis of Escherichia coli AlkB provides insight into substrate specificity and DNA damage searching. PLoS One. 2010 Jan 13;5(1):e8680. PMID:20084272 doi:10.1371/journal.pone.0008680
  7. ↑ Yang CG, Yi C, Duguid EM, Sullivan CT, Jian X, Rice PA, He C. Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA. Nature. 2008 Apr 24;452(7190):961-5. PMID:18432238 doi:http://dx.doi.org/10.1038/nature06889

3bi3, resolution 1.90Å

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