1eh8: Difference between revisions

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-{{Seed}}
-[[Image:1eh8.png|left|200px]]
-<!--
+==BENZYLATED HUMAN O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE==
-The line below this paragraph, containing "STRUCTURE_1eh8", creates the "Structure Box" on the page.
+<StructureSection load='1eh8' size='340' side='right'caption='[[1eh8]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1eh8]] is a 1 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=1EH8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EH8 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BCS:BENZYLCYSTEINE'>BCS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-{{STRUCTURE_1eh8|  PDB=1eh8  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1eh8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1eh8 OCA], [https://pdbe.org/1eh8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1eh8 RCSB], [https://www.ebi.ac.uk/pdbsum/1eh8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1eh8 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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 ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eh/1eh8_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=1eh8 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Human O(6)-alkylguanine-DNA alkyltransferase (AGT), which directly reverses endogenous alkylation at the O(6)-position of guanine, confers resistance to alkylation chemotherapies and is therefore an active anticancer drug target. Crystal structures of active human AGT and its biologically and therapeutically relevant methylated and benzylated product complexes reveal an unexpected zinc-stabilized helical bridge joining a two-domain alpha/beta structure. An asparagine hinge couples the active site motif to a helix-turn-helix (HTH) motif implicated in DNA binding. The reactive cysteine environment, its position within a groove adjacent to the alkyl-binding cavity and mutational analyses characterize DNA-damage recognition and inhibitor specificity, support a structure-based dealkylation mechanism and suggest a molecular basis for destabilization of the alkylated protein. These results support damaged nucleotide flipping facilitated by an arginine finger within the HTH motif to stabilize the extrahelical O(6)-alkylguanine without the protein conformational change originally proposed from the empty Ada structure. Cysteine alkylation sterically shifts the HTH recognition helix to evidently mechanistically couple release of repaired DNA to an opening of the protein fold to promote the biological turnover of the alkylated protein.
-===BENZYLATED HUMAN O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE===
+Active and alkylated human AGT structures: a novel zinc site, inhibitor and extrahelical base binding.,Daniels DS, Mol CD, Arvai AS, Kanugula S, Pegg AE, Tainer JA EMBO J. 2000 Apr 3;19(7):1719-30. PMID:10747039<ref>PMID:10747039</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1eh8" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_10747039}}, adds the Publication Abstract to the page
+*[[DNA methyltransferase 3D structures|DNA methyltransferase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 10747039 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_10747039}}
+__TOC__
+</StructureSection>
-==About this Structure==
-EH8 is a 1 chain 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=1EH8 OCA].
-==Reference==
-<ref group="xtra">PMID:10747039</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Daniels, D S.]]
+[[Category: Large Structures]]
-[[Category: Tainer, J A.]]
+[[Category: Daniels DS]]
-[[Category: Alkyltransferase]]
+[[Category: Tainer JA]]
-[[Category: Dna repair]]
-[[Category: Methyltransferase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 09:40:58 2009''