2i5w

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(New page: 200px<br /> <applet load="2i5w" size="450" color="white" frame="true" align="right" spinBox="true" caption="2i5w, resolution 2.60&Aring;" /> '''Structure of hOGG1 ...)
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[[Image:2i5w.gif|left|200px]]<br />
 
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<applet load="2i5w" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2i5w, resolution 2.60&Aring;" />
 
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'''Structure of hOGG1 crosslinked to DNA sampling a normal G adjacent to an oxoG'''<br />
 
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==Overview==
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==Structure of hOGG1 crosslinked to DNA sampling a normal G adjacent to an oxoG==
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How DNA glycosylases search through millions of base pairs and, discriminate between rare sites of damage and otherwise undamaged bases is, poorly understood. Even less understood are the details of the structural, states arising from DNA glycosylases interacting with undamaged DNA., Recognizing the mutagenic lesion 7,8-dihydro-8-oxoguanine (8-oxoguanine, oxoG) represents an especially formidable challenge, because this oxidized, nucleobase differs by only two atoms from its normal counterpart, guanine, (G), and buried in the structure of naked B-form DNA, oxoG and G are, practically indistinguishable from each other. We have used disulfide, cross-linking technology to capture a human oxoG repair protein, 8-oxoguanine DNA glycosylase I (hOGG1) sampling an undamaged G:C base pair, located adjacent to an oxoG:C base pair in DNA. The x-ray structure of the, trapped complex reveals that the presence of the 8-oxoG drastically, changes the local conformation of the extruded G. The extruded but, intrahelical state of the G in this structure offers a view of an early, intermediate in the base-extrusion pathway.
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<StructureSection load='2i5w' size='340' side='right'caption='[[2i5w]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2i5w]] 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=2I5W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I5W 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]] 2.6&#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=8OG:8-OXO-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>8OG</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=2i5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i5w OCA], [https://pdbe.org/2i5w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i5w RCSB], [https://www.ebi.ac.uk/pdbsum/2i5w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i5w ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/OGG1_HUMAN OGG1_HUMAN] Defects in OGG1 may be a cause of renal cell carcinoma (RCC) [MIM:[https://omim.org/entry/144700 144700]. It is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma.
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== Function ==
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[https://www.uniprot.org/uniprot/OGG1_HUMAN OGG1_HUMAN] DNA repair enzyme that incises DNA at 8-oxoG residues. Excises 7,8-dihydro-8-oxoguanine and 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine (FAPY) from damaged DNA. Has a beta-lyase activity that nicks DNA 3' to the lesion.
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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/i5/2i5w_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=2i5w ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known disease associated with this structure: Renal cell carcinoma, clear cell, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601982 601982]]
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*[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]]
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__TOC__
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==About this Structure==
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</StructureSection>
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2I5W is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2I5W OCA].
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==Reference==
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A nucleobase lesion remodels the interaction of its normal neighbor in a DNA glycosylase complex., Banerjee A, Verdine GL, Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15020-5. Epub 2006 Oct 2. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17015827 17015827]
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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: Banerjee, A.]]
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[[Category: Banerjee A]]
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[[Category: Verdine, G.L.]]
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[[Category: Verdine GL]]
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[[Category: CA]]
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[[Category: GOL]]
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[[Category: disulfide crosslink]]
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[[Category: dna glycosylase]]
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[[Category: protein-dna complex]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:41:26 2007''
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Current revision

Structure of hOGG1 crosslinked to DNA sampling a normal G adjacent to an oxoG

PDB ID 2i5w

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