title: Bacterial base excision repair enzyme Fpg recognizes bulky N7-substituted-FapydG lesion via unproductive binding mode.
abstract: Fpg is a bacterial base excision repair enzyme that removes oxidized purines from DNA. This work shows that Fpg and its eukaryote homolog Ogg1 recognize with high affinity FapydG and bulky N7-benzyl-FapydG (Bz-FapydG). The comparative crystal structure analysis of stable complexes between Fpg and carbocyclic cFapydG or Bz-cFapydG nucleoside-containing DNA provides the molecular basis of the ability of Fpg to bind both lesions with the same affinity and to differently process them. To accommodate the steric hindrance of the benzyl group, Fpg selects the adequate rotamer of the extrahelical Bz-cFapydG formamido group, forcing the bulky group to go outside the binding pocket. Contrary to the binding mode of cFapydG, the particular recognition of Bz-cFapydG leads the BER enzymes to unproductive complexes which would hide the lesion and slow down its repair by the NER machinery.
authors.affiliation: Centre de Biophysique Moléculaire, UPR4301, CNRS, rue Charles Sadron, 45071 Orléans cedex 02, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Coste
authors.forename: Matthias
authors.initials: M
authors.lastname: Ober
authors.forename: Yann-Vaï
authors.initials: YV
authors.lastname: Le Bihan
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Izquierdo
authors.forename: Nadège
authors.initials: N
authors.lastname: Hervouet
authors.forename: Heiko
authors.initials: H
authors.lastname: Mueller
authors.forename: Thomas
authors.initials: T
authors.lastname: Carell
authors.forename: Bertrand
authors.initials: B
authors.lastname: Castaing
mesh_terms: D000595:Amino Acid Sequence; D001671:Biochemistry / Q000379:methods; D045647:DNA Glycosylases / Q000737:chemistry / Q000378:metabolism; D004260:DNA Repair; D043382:DNA-Formamidopyrimidine Glycosylase / Q000737:chemistry / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D013237:Stereoisomerism
chemical_list: D029968:Escherichia coli Proteins; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D043382:DNA-Formamidopyrimidine Glycosylase; C468610:DNA-formamidopyrimidine glycosylase, E coli