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1lww

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(New page: 200px<br /> <applet load="1lww" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lww, resolution 2.1&Aring;" /> '''Borohydride-trapped ...)
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[[Image:1lww.gif|left|200px]]<br />
 
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<applet load="1lww" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1lww, resolution 2.1&Aring;" />
 
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'''Borohydride-trapped hOgg1 Intermediate Structure Co-Crystallized with 8-bromoguanine'''<br />
 
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==Overview==
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==Borohydride-trapped hOgg1 Intermediate Structure Co-Crystallized with 8-bromoguanine==
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Most spontaneous damage to bases in DNA is corrected through the action of, the base-excision DNA repair pathway. Base excision repair is initiated by, DNA glycosylases, lesion-specific enzymes that intercept aberrant bases in, DNA and catalyze their excision. How such proteins accomplish the feat of, catalyzing no fewer than five sequential reaction steps using a single, active site has been unknown. To help answer this, we report the structure, of a trapped catalytic intermediate in DNA repair by human 8-oxoguanine, DNA glycosylase. This structure and supporting biochemical results reveal, that the enzyme sequesters the excised lesion base and exploits it as a, cofactor to participate in catalysis. To our knowledge, the present, example represents the first documented case of product-assisted catalysis, in an enzyme-catalyzed reaction.
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<StructureSection load='1lww' size='340' side='right'caption='[[1lww]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1lww]] 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=1LWW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LWW 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]] 2.1&#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=BRG:8-BROMOGUANINE'>BRG</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PED:PENTANE-3,4-DIOL-5-PHOSPHATE'>PED</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=1lww FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lww OCA], [https://pdbe.org/1lww PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lww RCSB], [https://www.ebi.ac.uk/pdbsum/1lww PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lww 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/lw/1lww_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=1lww 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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1LWW 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 BRG as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1LWW OCA].
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==Reference==
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Product-assisted catalysis in base-excision DNA repair., Fromme JC, Bruner SD, Yang W, Karplus M, Verdine GL, Nat Struct Biol. 2003 Mar;10(3):204-11. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12592398 12592398]
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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: Bruner, S.D.]]
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[[Category: Bruner SD]]
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[[Category: Fromme, J.C.]]
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[[Category: Fromme JC]]
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[[Category: Karplus, M.]]
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[[Category: Karplus M]]
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[[Category: Verdine, G.L.]]
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[[Category: Verdine GL]]
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[[Category: Yang, W.]]
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[[Category: Yang W]]
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[[Category: BRG]]
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[[Category: CA]]
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[[Category: borohydride]]
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[[Category: covalent trapping]]
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[[Category: dna glycosylase]]
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[[Category: dna repair]]
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[[Category: product-assisted catalysis]]
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[[Category: protein/dna]]
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[[Category: reaction intermediate]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:04:45 2007''
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Current revision

Borohydride-trapped hOgg1 Intermediate Structure Co-Crystallized with 8-bromoguanine

PDB ID 1lww

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