1WYW

Crystal Structure of SUMO1-conjugated thymine DNA glycosylase

Summary for 1WYW

• Entry DOI: 10.2210/pdb1wyw/pdb
• Descriptor: G/T mismatch-specific thymine DNA glycosylase, Ubiquitin-like protein SMT3C, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q13569; Nucleus membrane: P63165
• Total number of polymer chains: 2
• Total formula weight: 37577.47

Authors

Baba, D.,Maita, N.,Jee, J.G.,Uchimura, Y.,Saitoh, H.,Sugasawa, K.,Hanaoka, F.,Tochio, H.,Hiroaki, H.,Shirakawa, M. (deposition date: 2005-02-17, release date: 2005-06-21, Last modification date: 2023-10-25)

Primary citation

Baba, D.,Maita, N.,Jee, J.G.,Uchimura, Y.,Saitoh, H.,Sugasawa, K.,Hanaoka, F.,Tochio, H.,Hiroaki, H.,Shirakawa, M.
Crystal structure of thymine DNA glycosylase conjugated to SUMO-1.
Nature, 435:979-982, 2005

PubMed Abstract: Members of the small ubiquitin-like modifier (SUMO) family can be covalently attached to the lysine residue of a target protein through an enzymatic pathway similar to that used in ubiquitin conjugation, and are involved in various cellular events that do not rely on degradative signalling via the proteasome or lysosome. However, little is known about the molecular mechanisms of SUMO-modification-induced protein functional transfer. During DNA mismatch repair, SUMO conjugation of the uracil/thymine DNA glycosylase TDG promotes the release of TDG from the abasic (AP) site created after base excision, and coordinates its transfer to AP endonuclease 1, which catalyses the next step in the repair pathway. Here we report the crystal structure of the central region of human TDG conjugated to SUMO-1 at 2.1 A resolution. The structure reveals a helix protruding from the protein surface, which presumably interferes with the product DNA and thus promotes the dissociation of TDG from the DNA molecule. This helix is formed by covalent and non-covalent contacts between TDG and SUMO-1. The non-covalent contacts are also essential for release from the product DNA, as verified by mutagenesis.

PubMed: 15959518
DOI: 10.1038/nature03634

Experimental method

X-RAY DIFFRACTION (2.1 Å)