DNA glycosylase

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[[Image:1akz.png|left|200px|thumb|Crystal Structure of DNA glycosylate, [[1akz]]]]
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<StructureSection load='' size='340' side='right' caption='Structure of adenine DNA glycosylase containing Fe4S4 cluster complex with DNA containing an oxoG base, deoxy-ribofuranose phosphate and Ca+2 ion (green) (PDB code [[1rrs]]).' scene='44/445369/Cv/1'>
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{{STRUCTURE_3fsp| PDB=3fsp | SIZE=400| SCENE= |right|CAPTION=Adenine DNA glycosylate complex with DNA, [[3fsp]] }}
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__TOC__
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== Function ==
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'''DNA glycosylase''' (DG) are enzymes which remove damaged DNA bases by flipping them out of the double helix followed by their cleavage. Monofunctional DG have only glycosylase activity; bifunctional DG also act as lysates; ADG, UDG, TDG remove adenine, uracil, thymine from DNA.<ref>PMID:15102448</ref><br />
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* '''Adenine DNA glycosylase''' is also called '''MutY'''. MutY has a role in prevention of DNA mutations resulting from oxidative damage forming the mutated base oxoG. DNA polymerase misreads oxoG and pairs it with adenine instead of cytosine. MutY removes adenine from the mismatched oxoG:A pair. MutY contains a 4Fe4S cluster.<br />
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* '''Uracil DNA glycosylase''' (UDG) eliminates uracil from DNA and thus preventing mutagenesis. UDG initiates the base excision repair pathway. UDG excises uracil in both AU and GU pairs. UDG can repair 10,000 damaged bases in the human cell per day<ref>PMID:9882380</ref>. See also [[DNA Repair]].
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* '''Thymine DNA glycosylase''' removes thymine moieties from mismatched G/T, C/T and T/T.<br />
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* '''Smug1''' is a single-strand selective monofunctional UDG. <br />
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* '''8-oxoguanine DNA glycosylase''' recognize oxidized bases.<br />
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* '''Human 8-oxoguanine''' GD is named hOgg1. See details on Ogg1 in [[8-Oxoguanine Glycosylase]].<br />
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* '''Methyladenine DNA glycosylase''' recognize methylated adenine; for details see [[Alka1]]. <br />
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* '''Formamidopyrimidine''' DG (FPG) or '''MutM''' or '''Fapy-DNA glycosylase''' removes oxidized purines from damaged DNA. More about FPG in<br />
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*[[Fpg Nei Protein Family]]<br />
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*[[Fpg Nei Protein Superfamily]].
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== Structural highlights ==
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MutY uses base flipping to twist the mispaired adenine out of the DNA helix and into the MutY active site. MutY contains 2 domains: C-terminal domain and catalytic domain containing a helix-hairpin-helix.
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*<scene name='44/445369/Cv/9'>Adenine DNA glycosylase containing Fe4S4 cluster with DNA containing an mispaired adenine 8OG and Ca+2</scene>.
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*<scene name='44/445369/Cv/10'>Mispaired adenine 8OG binding site</scene>.
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*<scene name='44/445369/Cv/11'>Fe4S4 cluster binds to 3 Cys residues</scene>.
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*<scene name='44/445369/Cv/12'>Ca+2 ion coordination site</scene> (PDB code [[1rrs]])<ref>PMID:14961129</ref>. Water molecules shown as red spheres.
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== 3D Structures of DNA glycosylase ==
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[[DNA glycosylase 3D structures]]
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</StructureSection>
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== References ==
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<references/>
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'''DNA glycosylase''' (DG) are enzymes which remove damaged DNA bases by flipping them out of the double helix followed by their cleavage. Monofunctional DG have only glycosylase activity; bifunctional DG also act as lysates; ADG, UDG, TDG remove adenine, uracil, thymine from DNA. ADG is also called MutY. Smug1 is a single-strand selective monofunctional UDG. OxDG recognize oxidized bases. The human 8-oxoguanine GD is named hOgg1. AlkDG recognize methylated adenine. Formamidopyrimidine DG (FPG) or MutM removes oxidized purines from damaged DNA. More about FPG in [[Fpg Nei Protein Family]] and [[Fpg Nei Protein Superfamily]].
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{{TOC limit|limit=2}}
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== 3D Structures of DNA glycosylate ==
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===Adenine DG===
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[[3n5n]] – hADG catalytic domain – human<BR />
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[[1yuo]] - hADG catalytic domain (mutant) <BR />
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[[1x51]] – hADG NUDIX domain - NMR<BR />
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[[3fsp]], [[3fsq]] – GsADG + DNA – ''Geobacillus stearothermophilus''<BR />
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[[3g0q]], [[1vrl]], [[1rrq]], [[1rrs]] - GsADG (mutant) + DNA – ''Bacillus stearothermophilus''<BR />
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[[1wef]], [[1weg]], [[1kg4]], [[1kg5]], [[1kg6]], [[1kg7]], [[1kqj]] - EcADG catalytic domain (mutant) - ''Escherichia coli''<BR />
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[[1kg2]], [[1kg3]], [[1muy]] - EcADG catalytic domain<BR />
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[[1mun]] - EcADG catalytic domain (mutant) <BR />
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[[1wei]], [[1mud]] - EcADG catalytic domain (mutant) + adenine
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===Uracil DG===
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[[3a7n]] – MtUDG – ''Mycobacterium tuberculosis''<BR />
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[[2zhx]] – MtDG + protein inhibitor<BR />
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[[1akz]] - hUDG (mutant) <BR />
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[[2oxm]], [[2oyt]], [[1q3f]] – hUDG + DNA<BR />
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[[1ssp]], [[2ssp]] - hUDG + DNA+ uracil<BR />
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[[1emh]], [[1emj]], [[4skn]] – hUDG (mutant) + DNA<BR />
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[[3fcf]], [[3fci]], [[3fck]], [[3fcl]], [[2hxm]] – hUDG + inhibitor<BR />
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[[1ugh]] - hUDG (mutant) + protein inhibitor<BR />
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[[2jhq]] – UDG – ''Vibrio cholerae''<BR />
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[[3cxm]] – UDG residues 129-373 + 5-bromo-uracil<BR />
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[[2owq]], [[2owr]] – UDG (mutant) – Vaccinia virus<BR />
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[[2d3y]], [[1ui0]], [[1ui1]] – TtUDG – ''Thermus thermophilus''<BR />
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[[2dp6]], [[2dem]], [[2ddg]] – TtUDG + DNA<BR />
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[[2j8x]] – UDG glycosylase domain + protein inhibitor – Epstein-Barr virus<BR />
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[[1lqj]] – EcUDG<BR />
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[[1flz]] - EcUDG (mutant) <BR />
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[[2eug]], [[3eug]], [[1eug]], [[4eug]], [[5eug]] - EcUDG (mutant) + uracil<BR />
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[[1mwj]], [[1mwi]], [[1mtl]] – EcUDG + DNA<BR />
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[[1lqg]], [[1lqm]], [[1eui]], [[1uug]] - EcUDG + protein inhibitor<BR />
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[[2uug]] - EcUDG (mutant) + protein inhibitor<BR />
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[[2c53]], [[2c56]] – HhUDG (mutant) – Human herpesvirus<BR />
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[[1lau]] – HhUDG + DNA<BR />
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[[1udh]], [[1udg]] – HsUDG _ Herpes simplex virus<BR />
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[[1udi]] - HsUDG + protein inhibitor<BR />
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[[2c2p]], [[2boo]] – DrUDG – ''Deinococcus radiodurans''<BR />
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[[2c2q]] – DrUDG (mutant) <BR />
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[[1vk2]], [[1l9g]] – TmUDG - ''Thermotoga maritime''<BR />
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[[1okb]] – UDG catalytic domain – Atlantic cod
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===Smug1 Uracil DG===
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[[1oe4]], [[1oe5]], [[1oe6]] – UDG Smug1 + DNA– Xenopus laevis
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===Thymine DG===
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[[2rba]] – hTDG core domain + DNA<BR />
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[[2d07]], [[1wyw]] – hTDG central region + SUMO-3<BR />
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[[1kea]] – TDG – ''Methanothermobacter thermautotrophicus''<BR />
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[[1mug]] – EcTDG
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===Human 8-oxoguanine DG===
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''Update June 2011''
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[[1ko9]] – hOgg1<BR />
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[[2xhi]], [[3ih7]], [[3ktu]], [[1hu0]], [[1fn7]] - hOgg1 + DNA<BR />
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[[1lwv]], [[1lww]], [[1lwy]] - hOgg1 + DNA<BR /> + guanine derivative<BR />
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[[2nob]], [[2noe]], [[2nof]], [[2noh]], [[2noi]], [[2nol]], [[2noz]], [[2i5w]], [[1yqk]], [[1yql]], [[1yqm]], [[1yqr]], [[1n39]], [[1n3a]], [[1n3c]] - hOgg1 (mutant) + DNA<BR />
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[[1m3h]], [[3ih7]] - hOgg1 core fragment (mutant) + DNA<BR />
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[[1m3q]], [[1ebm]] - hOgg1 core fragment (mutant) + DNA + guanine derivative
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===8-oxoguanine DG===
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[[3n0u]] – TmOxDG<BR />
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[[3knt]] - MjOxDG (mutant) + DNA – ''Methanocaldococcus jannaschii''<BR />
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[[3fhf]] - MjOxDG<BR />
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[[3go8]], [[3gp1]], [[3gpp]], [[3gpu]], [[3gpx]], [[3gpy]], [[3gq3]], [[3gq4]], [[3gq5]] – GsOxDG (mutant) + DNA<BR />
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[[3f0z]] - CaOxDG – ''Clostridium acetobutylicum''<BR />
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[[3f10]] – CaOxDG + 8-oxoguanosine<BR />
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[[3i0w]], [[3i0x]] - CaOxDG (mutant) + DNA<BR />
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[[3fhg]] - OxDG (mutant) – ''Sulfolobus solfataricus''<BR />
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[[1xqo]], [[1xqp]] – OxDG – ''Pyrobaculum aerophilum''
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===Methyladenine DG===
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[[3qi5]], [[1ewn]], [[1f4r]], [[1f6o]], [[1bnk]] – hAlkDG + DNA<BR />
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[[3bvs]] – BcAlkDG – ''Bacillus cereus''<BR />
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[[3jx7]], [[3jxy]], [[3jxz]], [[3jy1]] - BcAlkDG + DNA<BR />
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[[1pvs]], [[1p7m]], [[1mpg]] – EcAlkDG<BR />
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[[1nku]], [[1lmz]] – EcAlkDG - NMR<BR />
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[[3ogd]], [[3oh6]], [[3oh9]] - EcAlkDG (mutant) + DNA<BR />
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[[3d4v]], [[3cvs]], [[3cvt]], [[3cw7]], [[3cwa]], [[3cws]], [[3cwt]], [[3cwu]], [[1diz]] - EcAlkDG + DNA<BR />
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[[2ofk]] – StAlkDG – ''Salmonella typhi''<BR />
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[[2ofi]] – StAlkDG + DNA<BR />
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[[2jhj]], [[2jhn]] – AlkDG – ''Archaeoglobus fulgidus''<BR />
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[[2jg6]] – AlkDG – ''Staphylococcus aureus''<BR />
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[[1pu6]] – HpAlkDG – ''Helicobacter pylori''<BR />
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[[1pu7]], [[1pu8]] – HpAlkDG + adenine derivative
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===Formamidopyrimidine DG===
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[[3c58]], [[1xc8]], [[1tdz]], [[1pji]], [[1pm5]], [[1nnj]] - LlFpg+ DNA – ''Lactococcus lactis''<BR />
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[[1pjj]], [[1kfv]] - LlFpg (mutant) + DNA<BR />
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[[1k82]] - EcFpg+ DNA<BR />
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[[3jr4]], [[3jr5]], [[2f5n]], [[2f5o]], [[2f5p]], [[2f5q]], [[2f5s]], [[1r2y]], [[1r2z]] – GsFpg (mutant) + DNA<BR />
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[[1l1t]], [[1l1z]], [[1l2b]], [[1l2c]], [[1l2d]] - GsFpg + DNA<BR />
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[[3a42]], [[3a45]], [[3a46]] – Fpg – Acanthamoeba polyphaga minivirus<BR />
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[[2ea0]], [[2opf]], [[2oq4]], [[1k3w]], [[1k3x]] – EcGD NEI + DNA<BR />
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[[2fcc]] – Pyrimidine GD + DNA – Enterobacteria phage T4<br />
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[[1q39]] – EcGD NEI<br />
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[[1q3b]], [[1q3c]] – EcGD NEI (mutant)<br />
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[[1tdh]] – hGD NEI
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[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Structure of adenine DNA glycosylase containing Fe4S4 cluster complex with DNA containing an oxoG base, deoxy-ribofuranose phosphate and Ca+2 ion (green) (PDB code 1rrs).

Drag the structure with the mouse to rotate

References

  1. ↑ Fromme JC, Banerjee A, Verdine GL. DNA glycosylase recognition and catalysis. Curr Opin Struct Biol. 2004 Feb;14(1):43-9. PMID:15102448 doi:http://dx.doi.org/10.1016/j.sbi.2004.01.003
  2. ↑ Willetts KE, Rey F, Agostini I, Navarro JM, Baudat Y, Vigne R, Sire J. DNA repair enzyme uracil DNA glycosylase is specifically incorporated into human immunodeficiency virus type 1 viral particles through a Vpr-independent mechanism. J Virol. 1999 Feb;73(2):1682-8. PMID:9882380
  3. ↑ Fromme JC, Banerjee A, Huang SJ, Verdine GL. Structural basis for removal of adenine mispaired with 8-oxoguanine by MutY adenine DNA glycosylase. Nature. 2004 Feb 12;427(6975):652-6. PMID:14961129 doi:10.1038/nature02306

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Michal Harel, Alexander Berchansky, Joel L. Sussman, Jaime Prilusky

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