1yql
From Proteopedia
(New page: 200px<br /> <applet load="1yql" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yql, resolution 2.60Å" /> '''Catalytically inact...) |
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| - | [[Image:1yql.gif|left|200px]]<br /> | + | [[Image:1yql.gif|left|200px]]<br /><applet load="1yql" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1yql" size=" | + | |
caption="1yql, resolution 2.60Å" /> | caption="1yql, resolution 2.60Å" /> | ||
'''Catalytically inactive hOGG1 crosslinked with 7-deaza-8-azaguanine containing DNA'''<br /> | '''Catalytically inactive hOGG1 crosslinked with 7-deaza-8-azaguanine containing DNA'''<br /> | ||
==Overview== | ==Overview== | ||
| - | How DNA repair proteins distinguish between the rare sites of damage and | + | How DNA repair proteins distinguish between the rare sites of damage and the vast expanse of normal DNA is poorly understood. Recognizing the mutagenic lesion 8-oxoguanine (oxoG) represents an especially formidable challenge, because this oxidized nucleobase differs by only two atoms from its normal counterpart, guanine (G). Here we report the use of a covalent trapping strategy to capture a human oxoG repair protein, 8-oxoguanine DNA glycosylase I (hOGG1), in the act of interrogating normal DNA. The X-ray structure of the trapped complex features a target G nucleobase extruded from the DNA helix but denied insertion into the lesion recognition pocket of the enzyme. Free energy difference calculations show that both attractive and repulsive interactions have an important role in the preferential binding of oxoG compared with G to the active site. The structure reveals a remarkably effective gate-keeping strategy for lesion discrimination and suggests a mechanism for oxoG insertion into the hOGG1 active site. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1YQL 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 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1YQL 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> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YQL OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Banerjee, A.]] | [[Category: Banerjee, A.]] | ||
[[Category: Karplus, M.]] | [[Category: Karplus, M.]] | ||
| - | [[Category: Verdine, G | + | [[Category: Verdine, G L.]] |
[[Category: Yang, W.]] | [[Category: Yang, W.]] | ||
[[Category: CA]] | [[Category: CA]] | ||
[[Category: disulfide crosslinking]] | [[Category: disulfide crosslinking]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:08:05 2008'' |
Revision as of 14:08, 21 February 2008
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Catalytically inactive hOGG1 crosslinked with 7-deaza-8-azaguanine containing DNA
Contents |
Overview
How DNA repair proteins distinguish between the rare sites of damage and the vast expanse of normal DNA is poorly understood. Recognizing the mutagenic lesion 8-oxoguanine (oxoG) represents an especially formidable challenge, because this oxidized nucleobase differs by only two atoms from its normal counterpart, guanine (G). Here we report the use of a covalent trapping strategy to capture a human oxoG repair protein, 8-oxoguanine DNA glycosylase I (hOGG1), in the act of interrogating normal DNA. The X-ray structure of the trapped complex features a target G nucleobase extruded from the DNA helix but denied insertion into the lesion recognition pocket of the enzyme. Free energy difference calculations show that both attractive and repulsive interactions have an important role in the preferential binding of oxoG compared with G to the active site. The structure reveals a remarkably effective gate-keeping strategy for lesion discrimination and suggests a mechanism for oxoG insertion into the hOGG1 active site.
Disease
Known disease associated with this structure: Renal cell carcinoma, clear cell, somatic OMIM:[601982]
About this Structure
1YQL is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Structure of a repair enzyme interrogating undamaged DNA elucidates recognition of damaged DNA., Banerjee A, Yang W, Karplus M, Verdine GL, Nature. 2005 Mar 31;434(7033):612-8. PMID:15800616
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