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spinqualitylabelsall models PDB ID 1ua1 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 2.00Å
Ligands:	, , , , ,
Activity:	DNA-directed DNA polymerase, with EC number 2.7.7.7
Related:	1UA0
Resources:	FirstGlance, OCA, PDBsum, RCSB
Coordinates:	save as pdb, mmCIF, xml

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. 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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