5T2W

Structure of thymine DNA glycosylase bound to substrate analog 2'-F-5-formyl-dC

Summary for 5T2W

• Entry DOI: 10.2210/pdb5t2w/pdb
• Descriptor: G/T mismatch-specific thymine DNA glycosylase, DNA (28-MER), DNA (27-MER), ... (4 entities in total)
• Functional Keywords: protein-dna complex, hydrolase-dna complex, hydrolase/dna
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus : Q13569
• Total number of polymer chains: 3
• Total formula weight: 43118.09

Authors

Pidugu, L.S.,Pozharski, E.,Drohat, A.C. (deposition date: 2016-08-24, release date: 2016-11-09, Last modification date: 2023-10-04)

Primary citation

Pidugu, L.S.,Flowers, J.W.,Coey, C.T.,Pozharski, E.,Greenberg, M.M.,Drohat, A.C.
Structural Basis for Excision of 5-Formylcytosine by Thymine DNA Glycosylase.
Biochemistry, 55:6205-6208, 2016

PubMed Abstract: Thymine DNA glycosylase (TDG) is a base excision repair enzyme with key functions in epigenetic regulation. Performing a critical step in a pathway for active DNA demethylation, TDG removes 5-formylcytosine and 5-carboxylcytosine, oxidized derivatives of 5-methylcytosine that are generated by TET (ten-eleven translocation) enzymes. We determined a crystal structure of TDG bound to DNA with a noncleavable (2'-fluoroarabino) analogue of 5-formyldeoxycytidine flipped into its active site, revealing how it recognizes and hydrolytically excises fC. Together with previous structural and biochemical findings, the results illustrate how TDG employs an adaptable active site to excise a broad variety of nucleobases from DNA.

PubMed: 27805810
DOI: 10.1021/acs.biochem.6b00982

Experimental method

X-RAY DIFFRACTION (2.2 Å)