1x9m: Difference between revisions

From Proteopedia
Jump to navigationJump to search
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,615 edits
New page: left|200px<br /><applet load="1x9m" size="450" color="white" frame="true" align="right" spinBox="true" caption="1x9m, resolution 2.10Å" /> '''T7 DNA polymerase in...
 
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,615 edits
No edit summary
 
(15 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:1x9m.gif|left|200px]]<br /><applet load="1x9m" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1x9m, resolution 2.10&Aring;" />
'''T7 DNA polymerase in complex with an N-2-acetylaminofluorene-adducted DNA'''<br />


==Overview==
==T7 DNA polymerase in complex with an N-2-acetylaminofluorene-adducted DNA==
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 --&gt; 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 load='1x9m' size='340' side='right'caption='[[1x9m]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<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>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<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>
<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>
</table>
== 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>


==About this Structure==
==See Also==
1X9M is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bacteriophage_t7 Bacteriophage t7] and [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with MG as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1X9M OCA].
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
 
*[[Thioredoxin 3D structures|Thioredoxin 3D structures]]
==Reference==
__TOC__
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://ispc.weizmann.ac.il//pmbin/getpm?pmid=15528277 15528277]
</StructureSection>
[[Category: Bacteriophage t7]]
[[Category: DNA-directed DNA polymerase]]
[[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: MG]]
[[Category: Romano LJ]]
[[Category: dna ploymerase]]
[[Category: mutagenesis]]
[[Category: n-2-acetylaminofluorene]]
[[Category: replication block]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 05:55:08 2007''
Retrieved from "https://proteopedia.org/1x9m"