5ITT

Crystal Structure of Human NEIL1 bound to duplex DNA containing THF

Summary for 5ITT

• Entry DOI: 10.2210/pdb5itt/pdb
• Related: 5ITQ 5ITR 5ITU 5ITX 5ITY
• Descriptor: Endonuclease 8-like 1, DNA (26-MER), GLYCEROL, ... (5 entities in total)
• Functional Keywords: neil1 dna glycosylase base excision repair fpg nei, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome : Q96FI4
• Total number of polymer chains: 6
• Total formula weight: 158775.66

Authors

Zhu, C.,Lu, L.,Zhang, J.,Yue, Z.,Song, J.,Zong, S.,Liu, M.,Stovicek, O.,Gao, Y.,Yi, C. (deposition date: 2016-03-17, release date: 2016-07-06, Last modification date: 2023-11-08)

Primary citation

Zhu, C.,Lu, L.,Zhang, J.,Yue, Z.,Song, J.,Zong, S.,Liu, M.,Stovicek, O.,Gao, Y.Q.,Yi, C.
Tautomerization-dependent recognition and excision of oxidation damage in base-excision DNA repair
Proc.Natl.Acad.Sci.USA, 113:7792-7797, 2016

PubMed 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.

PubMed: 27354518
DOI: 10.1073/pnas.1604591113

Experimental method

X-RAY DIFFRACTION (2.53 Å)