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2xhi
From Proteopedia
(Difference between revisions)
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| - | + | ==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 == | |
| - | + | <table><tr><td colspan='2'>[[2xhi]] is a 3 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XHI FirstGlance]. <br> | |
| - | ==Disease== | + | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene><br> |
| + | <tr><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><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[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]]</td></tr> | ||
| + | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xhi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xhi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xhi RCSB], [http://www.ebi.ac.uk/pdbsum/2xhi PDBsum]</span></td></tr> | ||
| + | <table> | ||
| + | == Disease == | ||
[[http://www.uniprot.org/uniprot/OGG1_HUMAN OGG1_HUMAN]] Defects in OGG1 may be a cause of renal cell carcinoma (RCC) [MIM:[http://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. | [[http://www.uniprot.org/uniprot/OGG1_HUMAN OGG1_HUMAN]] Defects in OGG1 may be a cause of renal cell carcinoma (RCC) [MIM:[http://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== | + | |
[[http://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. | [[http://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> | ||
==See Also== | ==See Also== | ||
| - | *[[DNA | + | *[[DNA glycosylase|DNA glycosylase]] |
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| - | [[Category: | + | </StructureSection> |
| + | [[Category: Human]] | ||
[[Category: Alseth, I.]] | [[Category: Alseth, I.]] | ||
[[Category: Backe, P H.]] | [[Category: Backe, P H.]] | ||
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[[Category: Forstrom, R J.]] | [[Category: Forstrom, R J.]] | ||
[[Category: Helle, I H.]] | [[Category: Helle, I H.]] | ||
| - | [[Category: Vik, E S.]] | ||
[[Category: Dna repair]] | [[Category: Dna repair]] | ||
[[Category: Helix-hairpin-helix]] | [[Category: Helix-hairpin-helix]] | ||
[[Category: Lyase-dna complex]] | [[Category: Lyase-dna complex]] | ||
[[Category: Separation-of-function mutant]] | [[Category: Separation-of-function mutant]] | ||
Revision as of 07:14, 10 September 2014
Separation-of-function mutants unravel the dual reaction mode of human 8-oxoguanine DNA glycosylase
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