SNAP output for PDB entry 5itt [SNAP web server]

PDB-id

5itt; SNAP-derived features in text and JSON formats; DNAproDB

Class

DNA binding protein-DNA

Method

X-ray (2.53 Å)

Summary

Crystal structure of human neil1 bound to duplex DNA containing thf

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.