|
|
| Line 3: |
Line 3: |
| | <StructureSection load='2xhi' size='340' side='right'caption='[[2xhi]], [[Resolution|resolution]] 1.55Å' scene=''> | | <StructureSection load='2xhi' size='340' side='right'caption='[[2xhi]], [[Resolution|resolution]] 1.55Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2xhi]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. 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> | + | <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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | + | </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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=8OG:8-OXO-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>8OG</scene></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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2nof|2nof]], [[2noe|2noe]], [[2i5w|2i5w]], [[1lwv|1lwv]], [[1n39|1n39]], [[1fn7|1fn7]], [[2nol|2nol]], [[2noh|2noh]], [[1ko9|1ko9]], [[2nob|2nob]], [[1m3h|1m3h]], [[1hu0|1hu0]], [[1ebm|1ebm]], [[1n3a|1n3a]], [[1m3q|1m3q]], [[1lww|1lww]], [[1lwy|1lwy]], [[2noi|2noi]], [[2noz|2noz]], [[1n3c|1n3c]]</div></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> | | <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> | | </table> |
| | == Disease == | | == 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.
| + | [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 == | | == 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.
| + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 29: |
Line 28: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Alseth, I]] | + | [[Category: Alseth I]] |
| - | [[Category: Backe, P H]] | + | [[Category: Backe PH]] |
| - | [[Category: Bjoras, M]] | + | [[Category: Bjoras M]] |
| - | [[Category: Dalhus, B]] | + | [[Category: Dalhus B]] |
| - | [[Category: Forsbring, M]] | + | [[Category: Forsbring M]] |
| - | [[Category: Forstrom, R J]] | + | [[Category: Forstrom RJ]] |
| - | [[Category: Helle, I H]] | + | [[Category: Helle IH]] |
| - | [[Category: Dna repair]]
| + | |
| - | [[Category: Helix-hairpin-helix]]
| + | |
| - | [[Category: Lyase-dna complex]]
| + | |
| - | [[Category: Separation-of-function mutant]]
| + | |
| Structural highlights
Disease
OGG1_HUMAN Defects in OGG1 may be a cause of renal cell carcinoma (RCC) [MIM: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
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Dalhus B, Forsbring M, Helle IH, Vik ES, Forstrom RJ, Backe PH, Alseth I, Bjoras M. Separation-of-Function Mutants Unravel the Dual-Reaction Mode of Human 8-Oxoguanine DNA Glycosylase. Structure. 2011 Jan 12;19(1):117-27. PMID:21220122 doi:10.1016/j.str.2010.09.023
|
