Structural basis for arginine glycosylation of host substrates by bacterial effector proteins

Jun Bae Park, Young Hun Kim, Youngki Yoo, Juyeon Kim, Sung Hoon Jun, Jin Won Cho, Samir El Qaidi, Samuel Walpole, Serena Monaco, Ana A. García-García, Miaomiao Wu, Michael P. Hays, Ramon Hurtado-Guerrero, Jesus Angulo, Philip R. Hardwidge, Jeon Soo Shin, Hyun Soo Cho

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9 Citations (Scopus)


The bacterial effector proteins SseK and NleB glycosylate host proteins on arginine residues, leading to reduced NF-κB-dependent responses to infection. Salmonella SseK1 and SseK2 are E. coli NleB1 orthologs that behave as NleB1-like GTs, although they differ in protein substrate specificity. Here we report that these enzymes are retaining glycosyltransferases composed of a helix-loop-helix (HLH) domain, a lid domain, and a catalytic domain. A conserved HEN motif (His-Glu-Asn) in the active site is important for enzyme catalysis and bacterial virulence. We observe differences between SseK1 and SseK2 in interactions with substrates and identify substrate residues that are critical for enzyme recognition. Long Molecular Dynamics simulations suggest that the HLH domain determines substrate specificity and the lid-domain regulates the opening of the active site. Overall, our data suggest a front-face SNi mechanism, explain differences in activities among these effectors, and have implications for future drug development against enteric pathogens.

Original languageEnglish
Article number4283
JournalNature communications
Issue number1
Publication statusPublished - 2018 Dec 1


All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Park, J. B., Kim, Y. H., Yoo, Y., Kim, J., Jun, S. H., Cho, J. W., El Qaidi, S., Walpole, S., Monaco, S., García-García, A. A., Wu, M., Hays, M. P., Hurtado-Guerrero, R., Angulo, J., Hardwidge, P. R., Shin, J. S., & Cho, H. S. (2018). Structural basis for arginine glycosylation of host substrates by bacterial effector proteins. Nature communications, 9(1), [4283].