2oxm

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[[Image:2oxm.gif|left|200px]]<br /><applet load="2oxm" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2oxm, resolution 2.5&Aring;" />
 
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'''Crystal structure of a UNG2/modified DNA complex that represent a stabilized short-lived extrahelical state in ezymatic DNA base flipping'''<br />
 
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==Overview==
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==Crystal structure of a UNG2/modified DNA complex that represent a stabilized short-lived extrahelical state in ezymatic DNA base flipping==
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<StructureSection load='2oxm' size='340' side='right'caption='[[2oxm]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2oxm]] 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=2OXM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OXM FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4MF:1-(2-DEOXY-5-O-PHOSPHONO-BETA-D-ERYTHRO-PENTOFURANOSYL)-4-METHYL-1H-INDOLE'>4MF</scene></td></tr>
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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=2oxm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oxm OCA], [https://pdbe.org/2oxm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2oxm RCSB], [https://www.ebi.ac.uk/pdbsum/2oxm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2oxm ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/UNG_HUMAN UNG_HUMAN] Defects in UNG are a cause of immunodeficiency with hyper-IgM type 5 (HIGM5) [MIM:[https://omim.org/entry/608106 608106]. A rare immunodeficiency syndrome characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE. It results in a profound susceptibility to bacterial infections.<ref>PMID:12958596</ref> <ref>PMID:15967827</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/UNG_HUMAN UNG_HUMAN] Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine.
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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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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ox/2oxm_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=2oxm 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 ==
The enzyme uracil DNA glycosylase (UNG) excises unwanted uracil bases in the genome using an extrahelical base recognition mechanism. Efficient removal of uracil is essential for prevention of C-to-T transition mutations arising from cytosine deamination, cytotoxic U*A pairs arising from incorporation of dUTP in DNA, and for increasing immunoglobulin gene diversity during the acquired immune response. A central event in all of these UNG-mediated processes is the singling out of rare U*A or U*G base pairs in a background of approximately 10(9) T*A or C*G base pairs in the human genome. Here we establish for the human and Escherichia coli enzymes that discrimination of thymine and uracil is initiated by thermally induced opening of T*A and U*A base pairs and not by active participation of the enzyme. Thus, base-pair dynamics has a critical role in the genome-wide search for uracil, and may be involved in initial damage recognition by other DNA repair glycosylases.
The enzyme uracil DNA glycosylase (UNG) excises unwanted uracil bases in the genome using an extrahelical base recognition mechanism. Efficient removal of uracil is essential for prevention of C-to-T transition mutations arising from cytosine deamination, cytotoxic U*A pairs arising from incorporation of dUTP in DNA, and for increasing immunoglobulin gene diversity during the acquired immune response. A central event in all of these UNG-mediated processes is the singling out of rare U*A or U*G base pairs in a background of approximately 10(9) T*A or C*G base pairs in the human genome. Here we establish for the human and Escherichia coli enzymes that discrimination of thymine and uracil is initiated by thermally induced opening of T*A and U*A base pairs and not by active participation of the enzyme. Thus, base-pair dynamics has a critical role in the genome-wide search for uracil, and may be involved in initial damage recognition by other DNA repair glycosylases.
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==Disease==
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Enzymatic capture of an extrahelical thymine in the search for uracil in DNA.,Parker JB, Bianchet MA, Krosky DJ, Friedman JI, Amzel LM, Stivers JT Nature. 2007 Sep 27;449(7161):433-7. Epub 2007 Aug 19. PMID:17704764<ref>PMID:17704764</ref>
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Known diseases associated with this structure: Immunodeficiency with hyper IgM, type 4 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191525 191525]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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2OXM is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Known structural/functional Site: <scene name='pdbsite=AC1:4mf+Binding+Site+For+Residue+C+27'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OXM OCA].
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</div>
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<div class="pdbe-citations 2oxm" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Enzymatic capture of an extrahelical thymine in the search for uracil in DNA., Parker JB, Bianchet MA, Krosky DJ, Friedman JI, Amzel LM, Stivers JT, Nature. 2007 Sep 27;449(7161):433-7. Epub 2007 Aug 19. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17704764 17704764]
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*[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Amzel, L M.]]
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[[Category: Amzel LM]]
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[[Category: Bianchet, M A.]]
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[[Category: Bianchet MA]]
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[[Category: J T., Stivers.]]
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[[Category: Krosky DJ]]
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[[Category: Krosky, D J.]]
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[[Category: Stivers JT]]
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[[Category: enzyme dna complex]]
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[[Category: hydrolase/dna complex]]
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[[Category: ung2]]
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[[Category: uracil dna glycosylase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:23:41 2008''
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Current revision

Crystal structure of a UNG2/modified DNA complex that represent a stabilized short-lived extrahelical state in ezymatic DNA base flipping

PDB ID 2oxm

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