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Active site structure of the Shigella flexneri effector OspI

Nishide, A.; Takagi, K.; Kim, M.; Mizushima, T.

2022-02-15 biochemistry
10.1101/2022.02.15.480433 bioRxiv
Show abstract

Ubc13 is a critical ubiquitin-conjugating enzyme involved in the nuclear factor-{kappa}B (NF-{kappa}B) signalling pathway. The Shigella flexneri effector OspI targets the host Ubc13 and modifies this enzyme by deamidation of Gln100 into Glu100. This modification inhibits the tumour necrosis factor (TNF) receptor-associated factor 6 (TRAF6)-catalyzed ubiquitination and diacylglycerol-CBM (CARD-Bcl10- Malt1)-TRAF6-NF-{kappa}B signal activation. We have previously reported the wild-type OspI crystal structure, but the catalytic triad does not form the canonical active site. Here, the crystal structure of OspI with a C62S mutation was determined at a resolution of 2.2 [A]. This C62S mutant structure provided the active site conformation with the catalytic site of OspI.

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