1ua1

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spinqualitylabelsall models 1ua1, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Structure of aminofluorene adduct paired opposite cytosine at the polymerase active site.

Overview

Aromatic amines have been studied for more than a half-century as model, carcinogens representing a class of chemicals that form bulky adducts to, the C8 position of guanine in DNA. Among these guanine adducts, the, N-(2'-deoxyguanosin-8-yl)-aminofluorene (G-AF) and, N-2-(2'-deoxyguanosin-8-yl)-acetylaminofluorene (G-AAF) derivatives are, the best studied. Although G-AF and G-AAF differ by only an acetyl group, they exert different effects on DNA replication by replicative and, high-fidelity DNA polymerases. Translesion synthesis of G-AF is achieved, with high-fidelity polymerases, whereas replication of G-AAF requires, specialized bypass polymerases. Here we have presented structures of G-AF, as it undergoes one round of accurate replication by a high-fidelity DNA, polymerase. Nucleotide incorporation opposite G-AF is achieved in solution, and in the crystal, revealing how the polymerase accommodates and, replicates past G-AF, but not G-AAF. Like an unmodified guanine, G-AF, adopts a conformation that allows it to form Watson-Crick hydrogen bonds, with an opposing cytosine that results in protrusion of the bulky fluorene, moiety into the major groove. Although incorporation opposite G-AF is, observed, the C:G-AF base pair induces distortions to the polymerase, active site that slow translesion synthesis.

About this Structure

1UA1 is a Protein complex structure of sequences from Geobacillus stearothermophilus with SO4 and AF as ligands. Active as DNA-directed DNA polymerase, with EC number 2.7.7.7 Full crystallographic information is available from OCA.

Reference

Observing translesion synthesis of an aromatic amine DNA adduct by a high-fidelity DNA polymerase., Hsu GW, Kiefer JR, Burnouf D, Becherel OJ, Fuchs RP, Beese LS, J Biol Chem. 2004 Nov 26;279(48):50280-5. Epub 2004 Sep 22. PMID:15385534

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