title: Structural characterization of a mouse ortholog of human NEIL3 with a marked preference for single-stranded DNA.
abstract: Endonuclease VIII-like 3 (Neil3) is a DNA glycosylase of the base excision repair pathway that protects cells from oxidative DNA damage by excising a broad spectrum of cytotoxic and mutagenic base lesions. Interestingly, Neil3 exhibits an unusual preference for DNA with single-stranded regions. Here, we report the 2.0 Å crystal structure of a Neil3 enzyme. Although the glycosylase region of mouse Neil3 (MmuNeil3Δ324) exhibits the same overall fold as that of other Fpg/Nei proteins, it presents distinct structural features. First, MmuNeil3Δ324 lacks the αF-β9/10 loop that caps the flipped-out 8-oxoG in bacterial Fpg, which is consistent with its inability to cleave 8-oxoguanine. Second, Neil3 not only lacks two of the three void-filling residues that stabilize the opposite strand, but it also harbors negatively charged residues that create an unfavorable electrostatic environment for the phosphate backbone of that strand. These structural features provide insight into the substrate specificity and marked preference of Neil3 for ssDNA.
authors: Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405-0068, USA.
authors: Minmin
authors: M
authors: Liu
authors: Kayo
authors: K
authors: Imamura
authors: April M
authors: AM
authors: Averill
authors: Susan S
authors: SS
authors: Wallace
authors: Sylvie
authors: S
authors: Doublié
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004277:DNA, Single-Stranded / Q000737:chemistry*; D004706:Endodeoxyribonucleases / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D051379:Mice; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D013379:Substrate Specificity; D013499:Surface Properties
chemical_list: D004277:DNA, Single-Stranded; D004706:Endodeoxyribonucleases; C540052:NEIL3 protein, mouse