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PDB:1WYW

Protein Name

SUMO1-conjugated thymine DNA glycosylase

Species

Homo sapiens (human)

Biological Context

The blueprint of our body, DNA is continuously injured by environmental stresses. Damaged DNA can induce disorders such as cancer and senescence of the cells by wrong signal transmission. To avoid this kind of problem, we have several DNA repairing systems. One of the DNA repairing system is base excision repair. Uracil/thymine DNA glycosylase (TDG) is a DNA repairing enzyme that function in the first step of the base excision repair. After finding a mismatched thymine (or uracil), TDG excises the base. However, TDG does not release the DNA immediately. Because the abasic DNA, which is very unstable, can be cleaved, TDG protects the abasic site of the DNA until AP endonuclease, the next enzyme in the base excision repair, comes. This property is very rare in the variety of enzymes almost all of which quickly release the substrates after the enzymatic reactions. The novel property of TDG is explained by the modification of SUMO. SUMO is a protein which is similar in the structure to ubiquitin (a protein degradation signal protein), but "SUMOylation" of proteins does not induce protein degradation. Thus the significance of SUMO has been enigmatic.

Structure Description

1wyw1wyw_x1wyw_y

TDG contains an N-terminal DNA binding domain and a C-terminal SUMO binding domain. SUMO binds to the K330 in the SUMO binding domain. After the SUMOylation of TDG, an intermolecular beta-sheet is formed via the hydrogen bonds between SUMO binding domain of TDG and SUMO. This conformational change induces the collision of the C-terminal alpha-helix and the DNA; that results in substrate DNA release. This is the first example of the molecular switching mechanism regulated by SUMO.

Protein Data Bank (PDB)

References

Source

  • 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; (2005) 435:979-982. PubMed:15959518

Others

author: Daisuke Ino


Japanese version:PDB:1WYW