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1n3a

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Revision as of 08:44, 2 December 2020

Structural and biochemical exploration of a critical amino acid in human 8-oxoguanine glycosylase

Structural highlights

1n3a 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:	1ebm, 1fn7, 1ko9, 1n39
Gene:	OGG1 (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

Members of the HhH-GPD superfamily of DNA glycosylases are responsible for the recognition and removal of damaged nucleobases from DNA. The hallmark of these proteins is a motif comprising a helix-hairpin-helix followed by a Gly/Pro-rich loop and terminating in an invariant, catalytically essential aspartic acid residue. In this study, we have probed the role of this Asp in human 8-oxoguanine DNA glycosylase (hOgg1) by mutating it to Asn (D268N), Glu (D268E), and Gln (D268Q). We show that this aspartate plays a dual role, acting both as an N-terminal alpha-helix cap and as a critical residue for catalysis of both base excision and DNA strand cleavage by hOgg1. Mutation of this residue to asparagine, another helix-capping residue, preserves stability of the protein while drastically reducing enzymatic activity. A crystal structure of this mutant is the first to reveal the active site nucleophile Lys249 in the presence of lesion-containing DNA; this structure offers a tantalizing suggestion that base excision may occur by cleavage of the glycosidic bond and then attachment of Lys249. Mutation of the aspartic acid to glutamine and glutamic acid destabilizes the protein fold to a significant extent but, surprisingly, preserves catalytic activity. Crystal structures of these mutants complexed with an unreactive abasic site in DNA reveal these residues to adopt a sterically disfavored helix-capping conformation.

Structural and biochemical exploration of a critical amino acid in human 8-oxoguanine glycosylase.,Norman DP, Chung SJ, Verdine GL Biochemistry. 2003 Feb 18;42(6):1564-72. PMID:12578369^[1]

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

References

↑ Norman DP, Chung SJ, Verdine GL. Structural and biochemical exploration of a critical amino acid in human 8-oxoguanine glycosylase. Biochemistry. 2003 Feb 18;42(6):1564-72. PMID:12578369 doi:http://dx.doi.org/10.1021/bi026823d

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/1n3a"

@@ Line 1: / Line 1: @@
 ==Structural and biochemical exploration of a critical amino acid in human 8-oxoguanine glycosylase==
-<StructureSection load='1n3a' size='340' side='right' caption='[[1n3a]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+<StructureSection load='1n3a' size='340' side='right'caption='[[1n3a]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1n3a]] 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=1N3A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1N3A FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1n3a]] 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=1N3A OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1N3A FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
+</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>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=3DR:1,2-DIDEOXYRIBOFURANOSE-5-PHOSPHATE'>3DR</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ebm|1ebm]], [[1fn7|1fn7]], [[1ko9|1ko9]], [[1n39|1n39]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1ebm|1ebm]], [[1fn7|1fn7]], [[1ko9|1ko9]], [[1n39|1n39]]</div></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">OGG1 ([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=1n3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n3a OCA], [http://pdbe.org/1n3a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1n3a RCSB], [http://www.ebi.ac.uk/pdbsum/1n3a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1n3a ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1n3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n3a OCA], [http://pdbe.org/1n3a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1n3a RCSB], [http://www.ebi.ac.uk/pdbsum/1n3a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1n3a ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 33: / Line 33: @@
 </div>
 <div class="pdbe-citations 1n3a" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]]
 == References ==
 <references/>
@@ Line 38: / Line 41: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Chung, S J]]
 [[Category: Norman, D P]]

1n3a

From Proteopedia

Revision as of 08:44, 2 December 2020

Structural and biochemical exploration of a critical amino acid in human 8-oxoguanine glycosylase

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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