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| | ==REFINED STRUCTURE OF THE DNA METHYL PHOSPHOTRIESTER REPAIR DOMAIN OF E. COLI ADA== | | ==REFINED STRUCTURE OF THE DNA METHYL PHOSPHOTRIESTER REPAIR DOMAIN OF E. COLI ADA== |
| - | <StructureSection load='1eyf' size='340' side='right' caption='[[1eyf]], [[NMR_Ensembles_of_Models | 25 NMR models]]' scene=''> | + | <StructureSection load='1eyf' size='340' side='right'caption='[[1eyf]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1eyf]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EYF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1EYF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1eyf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EYF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EYF FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1adn|1adn]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1eyf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1eyf OCA], [http://pdbe.org/1eyf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1eyf RCSB], [http://www.ebi.ac.uk/pdbsum/1eyf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1eyf ProSAT]</span></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=1eyf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1eyf OCA], [https://pdbe.org/1eyf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1eyf RCSB], [https://www.ebi.ac.uk/pdbsum/1eyf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1eyf ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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 == | | == 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: Bacillus coli migula 1895]] | + | [[Category: Escherichia coli]] |
| - | [[Category: Dotsch, V]] | + | [[Category: Large Structures]] |
| - | [[Category: Lin, Y]] | + | [[Category: Dotsch V]] |
| - | [[Category: Myers, L C]] | + | [[Category: Lin Y]] |
| - | [[Category: Peariso, K]] | + | [[Category: Myers LC]] |
| - | [[Category: Penner-Hahn, J E]] | + | [[Category: Peariso K]] |
| - | [[Category: Verdine, G L]] | + | [[Category: Penner-Hahn JE]] |
| - | [[Category: Wagner, G]] | + | [[Category: Verdine GL]] |
| - | [[Category: Wintner, T]] | + | [[Category: Wagner G]] |
| - | [[Category: Dna binding protein]]
| + | [[Category: Wintner T]] |
| - | [[Category: One central beta-sheet sandwiched between two alpha-helice]]
| + | |
| Structural highlights
Function
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.[1] 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.[2]
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
The Escherichia coli protein Ada specifically repairs the S(p) diastereomer of DNA methyl phosphotriesters in DNA by direct and irreversible transfer of the methyl group to its own Cys 69 which is part of a zinc-thiolate center. The methyl transfer converts Ada into a transcriptional activator that binds sequence-specifically to promoter regions of its own gene and other methylation resistance genes. Ada thus acts as a chemosensor to activate repair mechanisms in situations of methylation damage. Here we present a highly refined solution structure of the 10 kDa N-terminal domain, N-Ada10, which reveals structural details of the nonspecific DNA interaction of N-Ada10 during the repair process and provides a basis for understanding the mechanism of the conformational switch triggered by methyl transfer. To further elucidate this, EXAFS (extended X-ray absorption fine structure) and XANES (X-ray absorption near-edge structure) data were acquired, which confirmed that the zinc-thiolate center is maintained when N-Ada is methylated. Thus, ligand exchange is not the mechanism that enhances sequence-specific DNA binding and transcriptional activation upon methylation of N-Ada. The mechanism of the switch was further elucidated by recording NOESY spectra of specifically labeled methylated-Ada/DNA complexes, which showed that the transferred methyl group makes many contacts within N-Ada but none with the DNA. This implies that methylation of N-Ada induces a structural change, which enhances the promoter affinity of a remodeled surface region that does not include the transferred methyl group.
Structural basis for the functional switch of the E. coli Ada protein.,Lin Y, Dotsch V, Wintner T, Peariso K, Myers LC, Penner-Hahn JE, Verdine GL, Wagner G Biochemistry. 2001 Apr 10;40(14):4261-71. PMID:11284682[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ McCarthy TV, Lindahl T. Methyl phosphotriesters in alkylated DNA are repaired by the Ada regulatory protein of E. coli. Nucleic Acids Res. 1985 Apr 25;13(8):2683-98. PMID:2987862
- ↑ McCarthy TV, Lindahl T. Methyl phosphotriesters in alkylated DNA are repaired by the Ada regulatory protein of E. coli. Nucleic Acids Res. 1985 Apr 25;13(8):2683-98. PMID:2987862
- ↑ Lin Y, Dotsch V, Wintner T, Peariso K, Myers LC, Penner-Hahn JE, Verdine GL, Wagner G. Structural basis for the functional switch of the E. coli Ada protein. Biochemistry. 2001 Apr 10;40(14):4261-71. PMID:11284682
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