5ITU: Crystal Structure Of Human Neil1(242k) Bound To Duplex Dna Containing Thf

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.
PDB ID: 5ITUDownload
MMDB ID: 141033
PDB Deposition Date: 2016/3/17
Updated in MMDB: 2016/08
Experimental Method:
x-ray diffraction
Resolution: 2.41  Å
Source Organism:
Similar Structures:
Biological Unit for 5ITU: trimeric; determined by author and by software (PISA)
Molecular Components in 5ITU
Label Count Molecule
Protein (1 molecule)
Endonuclease 8-like 1(Gene symbol: NEIL1)
Molecule annotation
Nucleotides(2 molecules)
DNA (5'-d(*cp*gp*tp*cp*cp*ap*cp*gp*tp*cp*tp*ap*c)-3')
Molecule annotation
DNA (5'-d(*tp*ap*gp*ap*cp*cp*tp*gp*gp*ap*cp*gp*g)-3')
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB