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| - | [[Image:1x9m.gif|left|200px]] | |
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| - | {{Structure
| + | ==T7 DNA polymerase in complex with an N-2-acetylaminofluorene-adducted DNA== |
| - | |PDB= 1x9m |SIZE=350|CAPTION= <scene name='initialview01'>1x9m</scene>, resolution 2.10Å
| + | <StructureSection load='1x9m' size='340' side='right'caption='[[1x9m]], [[Resolution|resolution]] 2.10Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=2DT:3'-DEOXYTHYMIDINE-5'-MONOPHOSPHATE'>2DT</scene>, <scene name='pdbligand=8FG:N-(5'-PHOSPHO-2'-DEOXYGUANOSIN-8-YL)-2-ACETYLAMINOFLUORENE'>8FG</scene>, <scene name='pdbligand=DA:2'-DEOXYADENOSINE-5'-MONOPHOSPHATE'>DA</scene>, <scene name='pdbligand=DC:2'-DEOXYCYTIDINE-5'-MONOPHOSPHATE'>DC</scene>, <scene name='pdbligand=DG:2'-DEOXYGUANOSINE-5'-MONOPHOSPHATE'>DG</scene>, <scene name='pdbligand=DT:THYMIDINE-5'-MONOPHOSPHATE'>DT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> | + | <table><tr><td colspan='2'>[[1x9m]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Escherichia_phage_T7 Escherichia phage T7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X9M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1X9M FirstGlance]. <br> |
| - | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] </span>
| + | </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> |
| - | |GENE= 5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10760 Enterobacteria phage T7]), trxA, tsnC, fipA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2DT:3-DEOXYTHYMIDINE-5-MONOPHOSPHATE'>2DT</scene>, <scene name='pdbligand=8FG:N-(5-PHOSPHO-2-DEOXYGUANOSIN-8-YL)-2-ACETYLAMINOFLUORENE'>8FG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | |DOMAIN=
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1x9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1x9m OCA], [https://pdbe.org/1x9m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1x9m RCSB], [https://www.ebi.ac.uk/pdbsum/1x9m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1x9m ProSAT]</span></td></tr> |
| - | |RELATEDENTRY=[[1t7p|1T7P]], [[1x9s|1X9S]], [[1x9w|1X9W]]
| + | </table> |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1x9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1x9m OCA], [http://www.ebi.ac.uk/pdbsum/1x9m PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1x9m RCSB]</span>
| + | == Function == |
| - | }}
| + | [https://www.uniprot.org/uniprot/THIO_ECOLI THIO_ECOLI] Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. |
| | + | == 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/x9/1x9m_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=1x9m ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | '''T7 DNA polymerase in complex with an N-2-acetylaminofluorene-adducted DNA'''
| + | ==See Also== |
| - | | + | *[[DNA polymerase 3D structures|DNA polymerase 3D structures]] |
| - | | + | *[[Thioredoxin 3D structures|Thioredoxin 3D structures]] |
| - | ==Overview== | + | __TOC__ |
| - | The carcinogen 2-acetylaminofluorene forms two major DNA adducts: N-(2'-deoxyguanosin-8-yl)-2-acetylaminofluorene (dG-AAF) and its deacetylated derivative, N-(2'-deoxyguanosin-8-yl)-2-aminofluorene (dG-AF). Although the dG-AAF and dG-AF adducts are distinguished only by the presence or absence of an acetyl group, they have profoundly different effects on DNA replication. dG-AAF poses a strong block to DNA synthesis and primarily induces frameshift mutations in bacteria, resulting in the loss of one or two nucleotides during replication past the lesion. dG-AF is less toxic and more easily bypassed by DNA polymerases, albeit with an increased frequency of misincorporation opposite the lesion, primarily resulting in G --> T transversions. We present three crystal structures of bacteriophage T7 DNA polymerase replication complexes, one with dG-AAF in the templating position and two others with dG-AF in the templating position. Our crystallographic data suggest why a dG-AAF adduct blocks replication more strongly than does a dG-AF adduct and provide a possible explanation for frameshift mutagenesis during replication bypass of a dG-AAF adduct. The dG-AAF nucleoside adopts a syn conformation that facilitates the intercalation of its fluorene ring into a hydrophobic pocket on the surface of the fingers subdomain and locks the fingers in an open, inactive conformation. In contrast, the dG-AF base at the templating position is not well defined by the electron density, consistent with weak binding to the polymerase and a possible interchange of this adduct between the syn and anti conformations.
| + | </StructureSection> |
| - | | + | |
| - | ==About this Structure==
| + | |
| - | 1X9M is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Enterobacteria_phage_t7 Enterobacteria phage t7] and [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X9M OCA].
| + | |
| - | | + | |
| - | ==Reference==
| + | |
| - | Crystal structures of 2-acetylaminofluorene and 2-aminofluorene in complex with T7 DNA polymerase reveal mechanisms of mutagenesis., Dutta S, Li Y, Johnson D, Dzantiev L, Richardson CC, Romano LJ, Ellenberger T, Proc Natl Acad Sci U S A. 2004 Nov 16;101(46):16186-91. Epub 2004 Nov 4. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15528277 15528277]
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| - | [[Category: DNA-directed DNA polymerase]]
| + | |
| - | [[Category: Enterobacteria phage t7]]
| + | |
| | [[Category: Escherichia coli]] | | [[Category: Escherichia coli]] |
| - | [[Category: Protein complex]] | + | [[Category: Escherichia phage T7]] |
| - | [[Category: Dutta, S.]] | + | [[Category: Large Structures]] |
| - | [[Category: Dzantiev, L.]] | + | [[Category: Dutta S]] |
| - | [[Category: Ellenberger, T.]] | + | [[Category: Dzantiev L]] |
| - | [[Category: Johnson, D.]] | + | [[Category: Ellenberger T]] |
| - | [[Category: Li, Y.]] | + | [[Category: Johnson D]] |
| - | [[Category: Richardson, C C.]] | + | [[Category: Li Y]] |
| - | [[Category: Romano, L J.]] | + | [[Category: Richardson CC]] |
| - | [[Category: dna ploymerase]]
| + | [[Category: Romano LJ]] |
| - | [[Category: mutagenesis]]
| + | |
| - | [[Category: n-2-acetylaminofluorene]]
| + | |
| - | [[Category: replication block]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:46:38 2008''
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