2hxm

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{{Seed}}
 
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[[Image:2hxm.png|left|200px]]
 
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==Complex of UNG2 and a small Molecule synthetic Inhibitor==
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The line below this paragraph, containing "STRUCTURE_2hxm", creates the "Structure Box" on the page.
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<StructureSection load='2hxm' size='340' side='right'caption='[[2hxm]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2hxm]] is a 1 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=2HXM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HXM FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 1.3&#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=302:4-[(1E,7E)-8-(2,6-DIOXO-1,2,3,6-TETRAHYDROPYRIMIDIN-4-YL)-3,6-DIOXA-2,7-DIAZAOCTA-1,7-DIEN-1-YL]BENZOIC+ACID'>302</scene></td></tr>
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{{STRUCTURE_2hxm| PDB=2hxm | SCENE= }}
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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=2hxm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hxm OCA], [https://pdbe.org/2hxm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hxm RCSB], [https://www.ebi.ac.uk/pdbsum/2hxm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hxm 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/hx/2hxm_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=2hxm 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 ==
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Human nuclear uracil DNA glycosylase (UNG2) is a cellular DNA repair enzyme that is essential for a number of diverse biological phenomena ranging from antibody diversification to B-cell lymphomas and type-1 human immunodeficiency virus infectivity. During each of these processes, UNG2 recognizes uracilated DNA and excises the uracil base by flipping it into the enzyme active site. We have taken advantage of the extrahelical uracil recognition mechanism to build large small-molecule libraries in which uracil is tethered via flexible alkane linkers to a collection of secondary binding elements. This high-throughput synthesis and screening approach produced two novel uracil-tethered inhibitors of UNG2, the best of which was crystallized with the enzyme. Remarkably, this inhibitor mimics the crucial hydrogen bonding and electrostatic interactions previously observed in UNG2 complexes with damaged uracilated DNA. Thus, the environment of the binding site selects for library ligands that share these DNA features. This is a general approach to rapid discovery of inhibitors of enzymes that recognize extrahelical damaged bases.
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===Complex of UNG2 and a small Molecule synthetic Inhibitor===
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Mimicking damaged DNA with a small molecule inhibitor of human UNG2.,Krosky DJ, Bianchet MA, Seiple L, Chung S, Amzel LM, Stivers JT Nucleic Acids Res. 2006;34(20):5872-9. Epub 2006 Oct 24. PMID:17062624<ref>PMID:17062624</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2hxm" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_17062624}}, adds the Publication Abstract to the page
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*[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 17062624 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_17062624}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2HXM is a [[Single protein]] structure of sequence 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=2HXM OCA].
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==Reference==
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Mimicking damaged DNA with a small molecule inhibitor of human UNG2., Krosky DJ, Bianchet MA, Seiple L, Chung S, Amzel LM, Stivers JT, Nucleic Acids Res. 2006;34(20):5872-9. Epub 2006 Oct 24. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17062624 17062624]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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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: Ghung, S.]]
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[[Category: Ghung S]]
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[[Category: Krosky, D J.]]
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[[Category: Krosky DJ]]
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[[Category: Seiple, L.]]
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[[Category: Seiple L]]
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[[Category: Stivers,J T.]]
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[[Category: Stivers JT]]
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[[Category: Dna repair]]
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[[Category: Uracil]]
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[[Category: Uracil dna glycosylase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 08:21:53 2008''
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Current revision

Complex of UNG2 and a small Molecule synthetic Inhibitor

PDB ID 2hxm

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