2i5w
From Proteopedia
(New page: 200px<br /> <applet load="2i5w" size="450" color="white" frame="true" align="right" spinBox="true" caption="2i5w, resolution 2.60Å" /> '''Structure of hOGG1 ...) |
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| - | [[Image:2i5w.gif|left|200px]]<br /> | + | [[Image:2i5w.gif|left|200px]]<br /><applet load="2i5w" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2i5w" size=" | + | |
caption="2i5w, resolution 2.60Å" /> | caption="2i5w, resolution 2.60Å" /> | ||
'''Structure of hOGG1 crosslinked to DNA sampling a normal G adjacent to an oxoG'''<br /> | '''Structure of hOGG1 crosslinked to DNA sampling a normal G adjacent to an oxoG'''<br /> | ||
==Overview== | ==Overview== | ||
| - | How DNA glycosylases search through millions of base pairs and | + | How DNA glycosylases search through millions of base pairs and discriminate between rare sites of damage and otherwise undamaged bases is poorly understood. Even less understood are the details of the structural states arising from DNA glycosylases interacting with undamaged DNA. Recognizing the mutagenic lesion 7,8-dihydro-8-oxoguanine (8-oxoguanine, oxoG) represents an especially formidable challenge, because this oxidized nucleobase differs by only two atoms from its normal counterpart, guanine (G), and buried in the structure of naked B-form DNA, oxoG and G are practically indistinguishable from each other. We have used disulfide cross-linking technology to capture a human oxoG repair protein, 8-oxoguanine DNA glycosylase I (hOGG1) sampling an undamaged G:C base pair located adjacent to an oxoG:C base pair in DNA. The x-ray structure of the trapped complex reveals that the presence of the 8-oxoG drastically changes the local conformation of the extruded G. The extruded but intrahelical state of the G in this structure offers a view of an early intermediate in the base-extrusion pathway. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2I5W is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2I5W is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I5W OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Banerjee, A.]] | [[Category: Banerjee, A.]] | ||
| - | [[Category: Verdine, G | + | [[Category: Verdine, G L.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: GOL]] | [[Category: GOL]] | ||
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[[Category: protein-dna complex]] | [[Category: protein-dna complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:49:25 2008'' |
Revision as of 15:49, 21 February 2008
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Structure of hOGG1 crosslinked to DNA sampling a normal G adjacent to an oxoG
Contents |
Overview
How DNA glycosylases search through millions of base pairs and discriminate between rare sites of damage and otherwise undamaged bases is poorly understood. Even less understood are the details of the structural states arising from DNA glycosylases interacting with undamaged DNA. Recognizing the mutagenic lesion 7,8-dihydro-8-oxoguanine (8-oxoguanine, oxoG) represents an especially formidable challenge, because this oxidized nucleobase differs by only two atoms from its normal counterpart, guanine (G), and buried in the structure of naked B-form DNA, oxoG and G are practically indistinguishable from each other. We have used disulfide cross-linking technology to capture a human oxoG repair protein, 8-oxoguanine DNA glycosylase I (hOGG1) sampling an undamaged G:C base pair located adjacent to an oxoG:C base pair in DNA. The x-ray structure of the trapped complex reveals that the presence of the 8-oxoG drastically changes the local conformation of the extruded G. The extruded but intrahelical state of the G in this structure offers a view of an early intermediate in the base-extrusion pathway.
Disease
Known disease associated with this structure: Renal cell carcinoma, clear cell, somatic OMIM:[601982]
About this Structure
2I5W is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
A nucleobase lesion remodels the interaction of its normal neighbor in a DNA glycosylase complex., Banerjee A, Verdine GL, Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15020-5. Epub 2006 Oct 2. PMID:17015827
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