5ity | pdb_00005ity

Crystal Structure of Human NEIL1(P2G) bound to duplex DNA containing Thymine Glycol

spinqualitylabelsall models 5ity, resolution 2.48Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ity is a 6 chain structure with sequence from Homo sapiens and Unidentified. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.48Å Ligands: CTG, GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NEIL1_HUMAN Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized pyrimidines, such as thymine glycol, formamidopyrimidine (Fapy) and 5-hydroxyuracil. Has marginal activity towards 8-oxoguanine. Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates. Has DNA glycosylase/lyase activity towards mismatched uracil and thymine, in particular in U:C and T:C mismatches. Publication Abstract from PubMed NEIL1 (Nei-like 1) is a DNA repair glycosylase guarding the mammalian genome against oxidized DNA bases. As the first enzymes in the base-excision repair pathway, glycosylases must recognize the cognate substrates and catalyze their excision. Here we present crystal structures of human NEIL1 bound to a range of duplex DNA. Together with computational and biochemical analyses, our results suggest that NEIL1 promotes tautomerization of thymine glycol (Tg)-a preferred substrate-for optimal binding in its active site. Moreover, this tautomerization event also facilitates NEIL1-catalyzed Tg excision. To our knowledge, the present example represents the first documented case of enzyme-promoted tautomerization for efficient substrate recognition and catalysis in an enzyme-catalyzed reaction. Tautomerization-dependent recognition and excision of oxidation damage in base-excision DNA repair.,Zhu C, Lu L, Zhang J, Yue Z, Song J, Zong S, Liu M, Stovicek O, Gao YQ, Yi C Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7792-7. doi:, 10.1073/pnas.1604591113. Epub 2016 Jun 27. PMID:27354518 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Endonuclease 3D structures

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