This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1x9m
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1x9m.gif|left|200px]] | [[Image:1x9m.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1x9m", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | + | --> | |
| - | + | {{STRUCTURE_1x9m| PDB=1x9m | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''T7 DNA polymerase in complex with an N-2-acetylaminofluorene-adducted DNA''' | '''T7 DNA polymerase in complex with an N-2-acetylaminofluorene-adducted DNA''' | ||
| Line 34: | Line 31: | ||
[[Category: Richardson, C C.]] | [[Category: Richardson, C C.]] | ||
[[Category: Romano, L J.]] | [[Category: Romano, L J.]] | ||
| - | [[Category: | + | [[Category: Dna ploymerase]] |
| - | [[Category: | + | [[Category: Mutagenesis]] |
| - | [[Category: | + | [[Category: N-2-acetylaminofluorene]] |
| - | [[Category: | + | [[Category: Replication block]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 14:44:59 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 an N-2-acetylaminofluorene-adducted DNA
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
1X9M 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 14:44:59 2008
