Summary information and primary citation

PDB-id
5ity; SNAP-derived features in text and JSON formats; DNAproDB
Class
DNA binding protein-DNA
Method
X-ray (2.48 Å)
Summary
Crystal structure of human neil1(p2g) bound to duplex DNA containing thymine glycol
Reference
Zhu C, Lu L, Zhang J, Yue Z, Song J, Zong S, Liu M, Stovicek O, Gao YQ, Yi C (2016): "Tautomerization-dependent recognition and excision of oxidation damage in base-excision DNA repair." Proc.Natl.Acad.Sci.USA, 113, 7792-7797. doi: 10.1073/pnas.1604591113.
Abstract
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.

Cartoon-block schematics in six views (download the tarball)

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