3TWM

Crystal structure of Arabidopsis thaliana FPG

Summary for 3TWM

• Entry DOI: 10.2210/pdb3twm/pdb
• Related: 3TWK 3TWL
• Descriptor: Formamidopyrimidine-DNA glycosylase 1, 5'-D(*AP*GP*CP*GP*TP*CP*CP*AP*(3DR)P*GP*TP*CP*TP*AP*CP*C)-3', 5'-D(*TP*GP*GP*TP*AP*GP*AP*CP*GP*TP*GP*GP*AP*CP*GP*C)-3', ... (4 entities in total)
• Functional Keywords: helix two turns helix, zinc-less finger, hydrolase, dna damage, dna repair, dna-binding, glycosidase, lyase, multifunctional enzyme, dna containing stable analog of abasic site, tetrahydro furan, hydrolase-dna complex, hydrolase/dna
• Biological source: Arabidopsis thaliana (mouse-ear cress, thale-cress); More
• Total number of polymer chains: 6
• Total formula weight: 88751.97

Authors

Duclos, S.,Aller, P.,Wallace, S.S.,Doublie, S. (deposition date: 2011-09-22, release date: 2012-07-25, Last modification date: 2023-09-13)

Primary citation

Duclos, S.,Aller, P.,Jaruga, P.,Dizdaroglu, M.,Wallace, S.S.,Doublie, S.
Structural and biochemical studies of a plant formamidopyrimidine-DNA glycosylase reveal why eukaryotic Fpg glycosylases do not excise 8-oxoguanine.
Dna Repair, 11:714-725, 2012

PubMed Abstract: Formamidopyrimidine-DNA glycosylase (Fpg; MutM) is a DNA repair enzyme widely distributed in bacteria. Fpg recognizes and excises oxidatively modified purines, 4,6-diamino-5-formamidopyrimidine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine and 8-oxoguanine (8-oxoG), with similar excision kinetics. It exhibits some lesser activity toward 8-oxoadenine. Fpg enzymes are also present in some plant and fungal species. The eukaryotic Fpg homologs exhibit little or no activity on DNA containing 8-oxoG, but they recognize and process its oxidation products, guanidinohydantoin (Gh) and spiroiminohydantoin (Sp). To date, several structures of bacterial Fpg enzymes unliganded or in complex with DNA containing a damaged base have been published but there is no structure of a eukaryotic Fpg. Here we describe the first crystal structure of a plant Fpg, Arabidopsis thaliana (AthFpg), unliganded and bound to DNA containing an abasic site analog, tetrahydrofuran (THF). Although AthFpg shares a common architecture with other Fpg glycosylases, it harbors a zincless finger, previously described in a subset of Nei enzymes, such as human NEIL1 and Mimivirus Nei1. Importantly the "αF-β9/10 loop" capping 8-oxoG in the active site of bacterial Fpg is very short in AthFpg. Deletion of a segment encompassing residues 213-229 in Escherichia coli Fpg (EcoFpg) and corresponding to the "αF-β9/10 loop" does not affect the recognition and removal of oxidatively damaged DNA base lesions, with the exception of 8-oxoG. Although the exact role of the loop remains to be further explored, it is now clear that this protein segment is specific to the processing of 8-oxoG.

PubMed: 22789755
DOI: 10.1016/j.dnarep.2012.06.004

Experimental method

X-RAY DIFFRACTION (2.8 Å)