title: Chemical shift assignments for human apurinic/apyrimidinic endonuclease 1.
abstract: Apurinic/apyrimidinic endonuclease 1 (APE1 or Ref-1) is the major enzyme in mammals for processing abasic sites in DNA. These cytotoxic and mutagenic lesions arise via spontaneous rupture of the base-sugar bond or the removal of damaged bases by a DNA glycosylase. APE1 cleaves the DNA backbone 5' to an abasic site, giving a 3'-OH primer for repair synthesis, and mediates other key repair activities. The DNA repair functions are essential for embryogenesis and cell viability. APE1-deficient cells are hypersensitive to DNA-damaging agents, and APE1 is considered an attractive target for inhibitors that could potentially enhance the efficacy of some anti-cancer agents. To enable an important new method for studying the structure, dynamics, catalytic mechanism, and inhibition of APE1, we assigned the chemical shifts (backbone and (13)C(beta)) of APE1 residues 39-318. We also report a protocol for refolding APE1, which was essential for achieving complete exchange of backbone amide sites for the perdeuterated protein.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland Baltimore, 108 N Greene St, Baltimore, MD 21201, USA.
authors.forename: Brittney A
authors.initials: BA
authors.lastname: Manvilla
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Varney
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Drohat
mesh_terms: D002247:Carbon Isotopes; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D008956:Models, Chemical; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D011336:Probability; D017510:Protein Folding; D012984:Software
chemical_list: D002247:Carbon Isotopes; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase