2xhi
From Proteopedia
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- | [[Image:2xhi.jpg|left|200px]] | ||
- | + | ==Separation-of-function mutants unravel the dual reaction mode of human 8-oxoguanine DNA glycosylase== | |
- | + | <StructureSection load='2xhi' size='340' side='right'caption='[[2xhi]], [[Resolution|resolution]] 1.55Å' scene=''> | |
- | + | == Structural highlights == | |
- | or the | + | <table><tr><td colspan='2'>[[2xhi]] 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=2XHI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XHI FirstGlance]. <br> |
- | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.55Å</td></tr> | |
- | --> | + | <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></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=2xhi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xhi OCA], [https://pdbe.org/2xhi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xhi RCSB], [https://www.ebi.ac.uk/pdbsum/2xhi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xhi ProSAT]</span></td></tr> | |
+ | </table> | ||
+ | == Disease == | ||
+ | [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. | ||
+ | == Function == | ||
+ | [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. | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | 7,8-Dihydro-8-oxoguanine (8oxoG) is a major mutagenic base lesion formed when reactive oxygen species react with guanine in DNA. The human 8oxoG DNA glycosylase (hOgg1) recognizes and initiates repair of 8oxoG. hOgg1 is acknowledged as a bifunctional DNA glycosylase catalyzing removal of the damaged base followed by cleavage of the backbone of the intermediate abasic DNA (AP lyase/beta-elimination). When acting on 8oxoG-containing DNA, these two steps in the hOgg1 catalysis are considered coupled, with Lys249 implicated as a key residue. However, several lines of evidence point to a concurrent and independent monofunctional hydrolysis of the N-glycosylic bond being the in vivo relevant reaction mode of hOgg1. Here, we present biochemical and structural evidence for the monofunctional mode of hOgg1 by design of separation-of-function mutants. Asp268 is identified as the catalytic residue, while Lys249 appears critical for the specific recognition and final alignment of 8oxoG during the hydrolysis reaction. | ||
- | + | Separation-of-Function Mutants Unravel the Dual-Reaction Mode of Human 8-Oxoguanine DNA Glycosylase.,Dalhus B, Forsbring M, Helle IH, Vik ES, Forstrom RJ, Backe PH, Alseth I, Bjoras M Structure. 2011 Jan 12;19(1):117-27. PMID:21220122<ref>PMID:21220122</ref> | |
+ | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
+ | </div> | ||
+ | <div class="pdbe-citations 2xhi" style="background-color:#fffaf0;"></div> | ||
- | + | ==See Also== | |
- | + | *[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]] | |
- | + | == References == | |
- | + | <references/> | |
- | + | __TOC__ | |
- | + | </StructureSection> | |
- | == | + | |
- | [[ | + | |
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- | == | + | |
- | < | + | |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
- | [[Category: Alseth | + | [[Category: Large Structures]] |
- | [[Category: Backe | + | [[Category: Alseth I]] |
- | [[Category: Bjoras | + | [[Category: Backe PH]] |
- | [[Category: Dalhus | + | [[Category: Bjoras M]] |
- | [[Category: Forsbring | + | [[Category: Dalhus B]] |
- | [[Category: Forstrom | + | [[Category: Forsbring M]] |
- | [[Category: Helle | + | [[Category: Forstrom RJ]] |
- | + | [[Category: Helle IH]] |
Current revision
Separation-of-function mutants unravel the dual reaction mode of human 8-oxoguanine DNA glycosylase
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Categories: Homo sapiens | Large Structures | Alseth I | Backe PH | Bjoras M | Dalhus B | Forsbring M | Forstrom RJ | Helle IH