8-Oxoguanine Glycosylase
From Proteopedia
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hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate(2). This motif is necessary for interacting with DNA to recognize and catalyze the substrate (5). | hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate(2). This motif is necessary for interacting with DNA to recognize and catalyze the substrate (5). | ||
| - | Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>Capelli et. al</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to discriminate between GO and G even though they differ at the C8 and N7 (the paper). hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref> Structure Vol.13, 87-98</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a catalytic pocket where residues lining the pocket can directly interact to excise the lesion (7,the paper). The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion. | + | Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>Capelli et. al</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to discriminate between GO and G even though they differ at the C8 and N7 (the paper). hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref> Structure Vol.13, 87-98</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion (7,the paper). The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion. |
=References= | =References= | ||
<references/> | <references/> | ||
Revision as of 21:14, 18 March 2010
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8-Oxoguanine Glycosylase
Contents |
Introduction
8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing genotoxic lesions caused by oxidative damage.
Function
hOGG1 repairs 7,8-dihydro-8-oxogunanine (8-oxoG, GO); this lesion is caused by oxidative attack from reactive species produced during normal metabolism. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 cleaves the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO that is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines.
Structure and Mechanism
hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate(2). This motif is necessary for interacting with DNA to recognize and catalyze the substrate (5).
Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell [1]. For this reason it is obvious that hOGG1 must have an efficient mechanism to discriminate between GO and G even though they differ at the C8 and N7 (the paper). hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a [2]. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a catalytic pocket where residues lining the pocket can directly interact to excise the lesion (7,the paper). The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion.
References
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