1t39

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{{Seed}}
 
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[[Image:1t39.png|left|200px]]
 
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==HUMAN O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE COVALENTLY CROSSLINKED TO DNA==
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The line below this paragraph, containing "STRUCTURE_1t39", creates the "Structure Box" on the page.
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<StructureSection load='1t39' size='340' side='right'caption='[[1t39]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<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>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3&#8491;</td></tr>
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<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>
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{{STRUCTURE_1t39| PDB=1t39 | SCENE= }}
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<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>
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</table>
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== Function ==
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[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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t3/1t39_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1t39 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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===HUMAN O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE COVALENTLY CROSSLINKED TO DNA===
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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<ref>PMID:15221026</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1t39" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_15221026}}, adds the Publication Abstract to the page
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*[[DNA methyltransferase 3D structures|DNA methyltransferase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 15221026 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_15221026}}
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__TOC__
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</StructureSection>
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==About this Structure==
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1T39 is a 6 chains structure of sequences 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=1T39 OCA].
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==Reference==
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<ref group="xtra">PMID:15221026</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Clarke, N D.]]
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[[Category: Large Structures]]
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[[Category: Daniels, D S.]]
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[[Category: Clarke ND]]
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[[Category: Luu, K X.]]
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[[Category: Daniels DS]]
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[[Category: Noll, D M.]]
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[[Category: Luu KX]]
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[[Category: Pegg, A E.]]
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[[Category: Noll DM]]
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[[Category: Tainer, J A.]]
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[[Category: Pegg AE]]
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[[Category: Woo, T T.]]
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[[Category: Tainer JA]]
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[[Category: Alkyltransferase]]
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[[Category: Woo TT]]
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[[Category: Dna repair]]
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[[Category: Helix-turn-helix]]
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[[Category: Methyltransferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 17:09:42 2009''
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Current revision

HUMAN O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE COVALENTLY CROSSLINKED TO DNA

PDB ID 1t39

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