1n3c
From Proteopedia
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| - | [[Image:1n3c.gif|left|200px]] | + | [[Image:1n3c.gif|left|200px]] |
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| - | '''Structural and biochemical exploration of a critical amino acid in human 8-oxoguanine glycosylase''' | + | {{Structure |
| + | |PDB= 1n3c |SIZE=350|CAPTION= <scene name='initialview01'>1n3c</scene>, resolution 2.70Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=CA:CALCIUM ION'>CA</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= OGG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Structural and biochemical exploration of a critical amino acid in human 8-oxoguanine glycosylase''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1N3C is a [ | + | 1N3C is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N3C OCA]. |
==Reference== | ==Reference== | ||
| - | 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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/12578369 12578369] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: hhh-gpd dna glycosylase dna repair oxoguanine]] | [[Category: hhh-gpd dna glycosylase dna repair oxoguanine]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:51:38 2008'' |
Revision as of 10:51, 20 March 2008
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| , resolution 2.70Å | |||||||
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| Ligands: | |||||||
| Gene: | OGG1 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structural and biochemical exploration of a critical amino acid in human 8-oxoguanine glycosylase
Contents |
Overview
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.
Disease
Known disease associated with this structure: Renal cell carcinoma, clear cell, somatic OMIM:[601982]
About this Structure
1N3C is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
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