Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-06680-6
Keywords
-
Categories
Funding
- National Research Foundation of Korea (NRF) - Korean government (MEST) [NRF-2016R1A2B2013305, 2016R1A5A1010764, 2014R1A4A1008625, 2017M3A9F6029755, 2017R1A2B3006704]
- Strategic Initiative for Microbiomes in Agriculture and Food - Ministry of Agriculture, Food and Rural Affairs [918012-4]
- Brain Korea 21 PLUS Project for Medical Science
- National Institutes of Health [AI093913, AI127973]
- ARAID
- MEC [CTQ2013-44367-C2-2-P, BFU2016-75633-P]
- DGA [E34_R17]
- School of Pharmacy of the University of East Anglia
- BBSRC [BB/P010660/1]
- DTP PhD studentship
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R21AI127973] Funding Source: NIH RePORTER
- Biotechnology and Biological Sciences Research Council [BB/P010660/1] Funding Source: researchfish
- BBSRC [1654460] Funding Source: UKRI
Ask authors/readers for more resources
The bacterial effector proteins SseK and NleB glycosylate host proteins on arginine residues, leading to reduced NF-kappa B-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 S(N)i mechanism, explain differences in activities among these effectors, and have implications for future drug development against enteric pathogens.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available