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| | <StructureSection load='1t39' size='340' side='right'caption='[[1t39]], [[Resolution|resolution]] 3.30Å' scene=''> | | <StructureSection load='1t39' size='340' side='right'caption='[[1t39]], [[Resolution|resolution]] 3.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1t39]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T39 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1T39 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1t39]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T39 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T39 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=E1X:PHOSPHORIC+ACID+MONO-[5-(1-ETHYL-2,6-DIOXO-1,2,3,6-TETRAHYDRO-PURIN-9-YL)-3-HYDROXY-TETRAHYDRO-FURAN-2-YLMETHYL]ESTER'>E1X</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1eh6|1eh6]], [[1eh7|1eh7]], [[1eh8|1eh8]], [[1t38|1t38]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=E1X:PHOSPHORIC+ACID+MONO-[5-(1-ETHYL-2,6-DIOXO-1,2,3,6-TETRAHYDRO-PURIN-9-YL)-3-HYDROXY-TETRAHYDRO-FURAN-2-YLMETHYL]ESTER'>E1X</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MGMT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1t39 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t39 OCA], [https://pdbe.org/1t39 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t39 RCSB], [https://www.ebi.ac.uk/pdbsum/1t39 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t39 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methylated-DNA--[protein]-cysteine_S-methyltransferase Methylated-DNA--[protein]-cysteine S-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.63 2.1.1.63] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1t39 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t39 OCA], [http://pdbe.org/1t39 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1t39 RCSB], [http://www.ebi.ac.uk/pdbsum/1t39 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1t39 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MGMT_HUMAN MGMT_HUMAN]] Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) in DNA. Repairs alkylated guanine in DNA by stoichiometrically transferring the alkyl group at the O-6 position to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated. | + | [https://www.uniprot.org/uniprot/MGMT_HUMAN MGMT_HUMAN] Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) in DNA. Repairs alkylated guanine in DNA by stoichiometrically transferring the alkyl group at the O-6 position to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Clarke, N D]] | + | [[Category: Clarke ND]] |
| - | [[Category: Daniels, D S]] | + | [[Category: Daniels DS]] |
| - | [[Category: Luu, K X]] | + | [[Category: Luu KX]] |
| - | [[Category: Noll, D M]] | + | [[Category: Noll DM]] |
| - | [[Category: Pegg, A E]] | + | [[Category: Pegg AE]] |
| - | [[Category: Tainer, J A]] | + | [[Category: Tainer JA]] |
| - | [[Category: Woo, T T]] | + | [[Category: Woo TT]] |
| - | [[Category: Alkyltransferase]]
| + | |
| - | [[Category: Dna repair]]
| + | |
| - | [[Category: Helix-turn-helix]]
| + | |
| - | [[Category: Methyltransferase]]
| + | |
| - | [[Category: Transferase-dna complex]]
| + | |
| Structural highlights
Function
MGMT_HUMAN Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) in DNA. Repairs alkylated guanine in DNA by stoichiometrically transferring the alkyl group at the O-6 position to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
O(6)-alkylguanine-DNA alkyltransferase (AGT), or O(6)-methylguanine-DNA methyltransferase (MGMT), prevents mutations and apoptosis resulting from alkylation damage to guanines. AGT irreversibly transfers the alkyl lesion to an active site cysteine in a stoichiometric, direct damage reversal pathway. AGT expression therefore elicits tumor resistance to alkylating chemotherapies, and AGT inhibitors are in clinical trials. We report here structures of human AGT in complex with double-stranded DNA containing the biological substrate O(6)-methylguanine or crosslinked to the mechanistic inhibitor N(1),O(6)-ethanoxanthosine. The prototypical DNA major groove-binding helix-turn-helix (HTH) motif mediates unprecedented minor groove DNA binding. This binding architecture has advantages for DNA repair and nucleotide flipping, and provides a paradigm for HTH interactions in sequence-independent DNA-binding proteins like RecQ and BRCA2. Structural and biochemical results further support an unpredicted role for Tyr114 in nucleotide flipping through phosphate rotation and an efficient kinetic mechanism for locating alkylated bases.
DNA binding and nucleotide flipping by the human DNA repair protein AGT.,Daniels DS, Woo TT, Luu KX, Noll DM, Clarke ND, Pegg AE, Tainer JA Nat Struct Mol Biol. 2004 Aug;11(8):714-20. Epub 2004 Jun 27. PMID:15221026[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Daniels DS, Woo TT, Luu KX, Noll DM, Clarke ND, Pegg AE, Tainer JA. DNA binding and nucleotide flipping by the human DNA repair protein AGT. Nat Struct Mol Biol. 2004 Aug;11(8):714-20. Epub 2004 Jun 27. PMID:15221026 doi:10.1038/nsmb791
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