1x9w
From Proteopedia
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[[Image:1x9w.gif|left|200px]] | [[Image:1x9w.gif|left|200px]] | ||
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'''T7 DNA polymerase in complex with a primer/template DNA containing a disordered N-2 aminofluorene on the template, crystallized with dideoxy-ATP as the incoming nucleotide.''' | '''T7 DNA polymerase in complex with a primer/template DNA containing a disordered N-2 aminofluorene on the template, crystallized with dideoxy-ATP as the incoming nucleotide.''' | ||
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[[Category: Richardson, C C.]] | [[Category: Richardson, C C.]] | ||
[[Category: Romano, L J.]] | [[Category: Romano, L J.]] | ||
| - | [[Category: | + | [[Category: Dna polymerase]] |
| - | [[Category: | + | [[Category: Mutagenesis]] |
| - | [[Category: | + | [[Category: N-2-aminofluorene]] |
| - | [[Category: | + | [[Category: Replication block]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 14:45:32 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 11:45, 3 May 2008
T7 DNA polymerase in complex with a primer/template DNA containing a disordered N-2 aminofluorene on the template, crystallized with dideoxy-ATP as the incoming nucleotide.
Overview
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.
About this Structure
1X9W is a Protein complex structure of sequences from Enterobacteria phage t7 and Escherichia coli. Full crystallographic information is available from 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:15528277 Page seeded by OCA on Sat May 3 14:45:32 2008
