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From Proteopedia
Crystal structure of mouse Endonuclease VIII-LIKE 3 (mNEIL3)
Structural highlights
Function[NEIL3_MOUSE] DNA glycosylase which prefers single-stranded DNA (ssDNA), or partially ssDNA structures such as bubble and fork structures, to double-stranded DNA (dsDNA). In vitro, displays strong glycosylase activity towards the hydantoin lesions spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh) in both ssDNA and dsDNA; also recognizes FapyA, FapyG, 5-OHU, 5-OHC, 5-OHMH, Tg and 8-oxoA lesions in ssDNA. No activity on 8-oxoG detected. Also shows weak DNA-(apurinic or apyrimidinic site) lyase activity. In vivo, appears to be the primary enzyme involved in removing Sp and Gh from ssDNA in neonatal tissues. Seems to be an important facilitator of cell proliferation in certain populations, for example neural stem/progenitor cells and tumor cells, suggesting a role in replication-associated DNA repair.[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedEndonuclease 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 A crystal structure of a Neil3 enzyme. Although the glycosylase region of mouse Neil3 (MmuNeil3Delta324) exhibits the same overall fold as that of other Fpg/Nei proteins, it presents distinct structural features. First, MmuNeil3Delta324 lacks the alphaF-beta9/10 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. Structural Characterization of a Mouse Ortholog of Human NEIL3 with a Marked Preference for Single-Stranded DNA.,Liu M, Imamura K, Averill AM, Wallace SS, Doublie S Structure. 2013 Feb 5;21(2):247-56. doi: 10.1016/j.str.2012.12.008. Epub 2013 Jan, 9. PMID:23313161[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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