1u8b
From Proteopedia
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| - | [[Image:1u8b.gif|left|200px]]<br /><applet load="1u8b" size="350" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="1u8b, resolution 2.10Å" /> | ||
| - | '''Crystal structure of the methylated N-ADA/DNA complex'''<br /> | ||
| - | == | + | ==Crystal structure of the methylated N-ADA/DNA complex== |
| + | <StructureSection load='1u8b' size='340' side='right'caption='[[1u8b]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[1u8b]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U8B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1U8B FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SMC:S-METHYLCYSTEINE'>SMC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=1u8b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u8b OCA], [https://pdbe.org/1u8b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1u8b RCSB], [https://www.ebi.ac.uk/pdbsum/1u8b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1u8b ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ADA_ECOLI ADA_ECOLI] Is involved in the adaptive response to alkylation damage in DNA caused by alkylating agents. Repairs O6-methylguanine and 04-methylthymine residues in alkylated DNA by a direct and irreversible transfer of the methyl group from the base to one of its own cysteine residues (Cys-321). Also specifically repairs the Sp diastereomer of DNA methylphosphotriester lesions by the same mechanism, although the methyl transfer occurs onto a different cysteine residue (Cys-38). Can not demethylate the other diastereomer, Rp-methylphosphotriester.<ref>PMID:2987862</ref> The methylation of Ada by methylphosphotriesters in DNA leads to its activation as a transcriptional regulator that activates the transcription of its own gene, ada, and other alkylation resistance genes, alkA, alkB and aidB.<ref>PMID:2987862</ref> | ||
| + | == 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/u8/1u8b_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1u8b ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
The transcriptional activity of many sequence-specific DNA binding proteins is directly regulated by posttranslational covalent modification. Although this form of regulation was first described nearly two decades ago, it remains poorly understood at a mechanistic level. The prototype for a transcription factor controlled by posttranslational modification is E. coli Ada protein, a chemosensor that both repairs methylation damage in DNA and coordinates the resistance response to genotoxic methylating agents. Ada repairs methyl phosphotriester lesions in DNA by transferring the aberrant methyl group to one of its own cysteine residues; this site-specific methylation enhances tremendously the DNA binding activity of the protein, thereby enabling it to activate a methylation-resistance regulon. Here, we report solution and X-ray structures of the Cys-methylated chemosensor domain of Ada bound to DNA. The structures reveal that both phosphotriester repair and methylation-dependent transcriptional activation function through a zinc- and methylation-dependent electrostatic switch. | The transcriptional activity of many sequence-specific DNA binding proteins is directly regulated by posttranslational covalent modification. Although this form of regulation was first described nearly two decades ago, it remains poorly understood at a mechanistic level. The prototype for a transcription factor controlled by posttranslational modification is E. coli Ada protein, a chemosensor that both repairs methylation damage in DNA and coordinates the resistance response to genotoxic methylating agents. Ada repairs methyl phosphotriester lesions in DNA by transferring the aberrant methyl group to one of its own cysteine residues; this site-specific methylation enhances tremendously the DNA binding activity of the protein, thereby enabling it to activate a methylation-resistance regulon. Here, we report solution and X-ray structures of the Cys-methylated chemosensor domain of Ada bound to DNA. The structures reveal that both phosphotriester repair and methylation-dependent transcriptional activation function through a zinc- and methylation-dependent electrostatic switch. | ||
| - | + | A methylation-dependent electrostatic switch controls DNA repair and transcriptional activation by E. coli ada.,He C, Hus JC, Sun LJ, Zhou P, Norman DP, Dotsch V, Wei H, Gross JD, Lane WS, Wagner G, Verdine GL Mol Cell. 2005 Oct 7;20(1):117-29. PMID:16209950<ref>PMID:16209950</ref> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 1u8b" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: Dotsch | + | [[Category: Dotsch V]] |
| - | [[Category: Gross | + | [[Category: Gross JD]] |
| - | [[Category: He | + | [[Category: He C]] |
| - | [[Category: Hus | + | [[Category: Hus J-C]] |
| - | [[Category: Lane | + | [[Category: Lane WS]] |
| - | [[Category: Norman | + | [[Category: Norman DPG]] |
| - | [[Category: Sun | + | [[Category: Sun LJ]] |
| - | [[Category: Verdine | + | [[Category: Verdine GL]] |
| - | [[Category: Wagner | + | [[Category: Wagner G]] |
| - | [[Category: Zhou | + | [[Category: Zhou P]] |
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Current revision
Crystal structure of the methylated N-ADA/DNA complex
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Categories: Escherichia coli | Large Structures | Dotsch V | Gross JD | He C | Hus J-C | Lane WS | Norman DPG | Sun LJ | Verdine GL | Wagner G | Zhou P
