NleB/SseK-catalyzed arginine-glycosylation and enteropathogen virulence are finely tuned by a single variable position contiguous to the catalytic machinery.

ABSTRACT: NleB/SseK effectors are arginine-GlcNAc-transferases expressed by enteric bacterial pathogens that modify host cell proteins to disrupt signaling pathways. While the conserved Citrobacter rodentium NleB and E. coli NleB1 proteins display a broad selectivity towards host proteins, Salmonella enterica SseK1, SseK2, and SseK3 have a narrowed protein substrate selectivity. Here, by combining computational and biophysical experiments, we demonstrate that the broad protein substrate selectivity of NleB relies on Tyr284^NleB/NleB1, a second-shell residue contiguous to the catalytic machinery. Tyr284^NleB/NleB1 is important in coupling protein substrate binding to catalysis. This is exemplified by S286Y^SseK1 and N302Y^SseK2 mutants, whi

SUBMITTER: Garcia-Garcia A 

PROVIDER: S-EPMC8457375 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature