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2noe

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Revision as of 08:37, 18 October 2017

Structure of catalytically inactive G42A human 8-oxoguanine glycosylase complexed to 8-oxoguanine DNA

Structural highlights

2noe is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Related:	1ko9, 1ebm, 1yqk, 1yqr, 1fn7, 1n3c, 2nob, 2nof, 2noh, 2noi, 2nol, 2noz
Gene:	OGG1, MMH, MUTM, OGH1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The human 8-oxoguanine DNA glycosylase (hOGG1) protein is responsible for initiating base excision DNA repair of the endogenous mutagen 8-oxoguanine. Like nearly all DNA glycosylases, hOGG1 extrudes its substrate from the DNA helix and inserts it into an extrahelical enzyme active site pocket lined with residues that participate in lesion recognition and catalysis. Structural analysis has been performed on mutant versions of hOGG1 having changes in catalytic residues but not on variants having altered 7,8-dihydro-8-oxoguanine (oxoG) contact residues. Here we report high resolution structural analysis of such recognition variants. We found that Ala substitution at residues that contact the phosphate 5' to the lesion (H270A mutation) and its Watson-Crick face (Q315A mutation) simply removed key functionality from the contact interface but otherwise had no effect on structure. Ala substitution at the only residue making an oxoG-specific contact (G42A mutation) introduced torsional stress into the DNA contact surface of hOGG1, but this was overcome by local interactions within the folded protein, indicating that this oxoG recognition motif is "hardwired." Introduction of a side chain intended to sterically obstruct the active site pocket (Q315F mutation) led to two different structures, one of which (Q315F(*149)) has the oxoG lesion in an exosite flanking the active site and the other of which (Q315F(*292)) has the oxoG inserted nearly completely into the lesion recognition pocket. The latter structure offers a view of the latest stage in the base extrusion pathway yet observed, and its lack of catalytic activity demonstrates that the transition state for displacement of the lesion base is geometrically demanding.

Structural characterization of human 8-oxoguanine DNA glycosylase variants bearing active site mutations.,Radom CT, Banerjee A, Verdine GL J Biol Chem. 2007 Mar 23;282(12):9182-94. Epub 2006 Nov 16. PMID:17114185^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Radom CT, Banerjee A, Verdine GL. Structural characterization of human 8-oxoguanine DNA glycosylase variants bearing active site mutations. J Biol Chem. 2007 Mar 23;282(12):9182-94. Epub 2006 Nov 16. PMID:17114185 doi:http://dx.doi.org/10.1074/jbc.M608989200

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2noe"

@@ Line 1: / Line 1: @@
 ==Structure of catalytically inactive G42A human 8-oxoguanine glycosylase complexed to 8-oxoguanine DNA==
 <StructureSection load='2noe' size='340' side='right' caption='[[2noe]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ko9|1ko9]], [[1ebm|1ebm]], [[1yqk|1yqk]], [[1yqr|1yqr]], [[1fn7|1fn7]], [[1n3c|1n3c]], [[2nob|2nob]], [[2nof|2nof]], [[2noh|2noh]], [[2noi|2noi]], [[2nol|2nol]], [[2noz|2noz]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">OGG1, MMH, MUTM, OGH1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2noe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2noe OCA], [http://pdbe.org/2noe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2noe RCSB], [http://www.ebi.ac.uk/pdbsum/2noe PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2noe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2noe OCA], [http://pdbe.org/2noe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2noe RCSB], [http://www.ebi.ac.uk/pdbsum/2noe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2noe ProSAT]</span></td></tr>
 </table>
 == Disease ==

2noe

From Proteopedia

Revision as of 08:37, 18 October 2017

Structure of catalytically inactive G42A human 8-oxoguanine glycosylase complexed to 8-oxoguanine DNA

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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