@article{f82d89eba5674ea2afa5ce0d6d0a37c5,
title = "Structural and mechanistic investigations of protein S-glycosyltransferases",
abstract = "Attachment of sugars to nitrogen and oxygen in peptides is ubiquitous in biology, but glycosylation of sulfur atoms has only been recently described. Here, we characterize two S-glycosyltransferases SunS and ThuS that selectively glycosylate one of five Cys residues in their substrate peptides; substitution of this Cys with Ser results in a strong decrease in glycosylation activity. Crystal structures of SunS and ThuS in complex with UDP-glucose or a derivative reveal an unusual architecture in which a glycosyltransferase type A (GTA) fold is decorated with additional domains to support homodimerization. Dimer formation creates an extended cavity for the substrate peptide, drawing functional analogy with O-glycosyltransferases involved in cell wall biosynthesis. This extended cavity contains a sharp bend that may explain the site selectivity of the glycosylation because the target Cys is in a Gly-rich stretch that can accommodate the bend. These studies establish a molecular framework for understanding the unusual S-glycosyltransferases.",
keywords = "glycocin, bacteriocin, antibiotic, RiPPs, S-glycosyltransferase, crystallography, S-glycosylation",
author = "Daisuke Fujinami and {Garcia de Gonzalo}, {Chantal V} and Subhanip Biswas and Yue Hao and Huan Wang and Neha Garg and Tiit Lukk and Nair, {Satish K} and {van der Donk}, {Wilfred A}",
note = "Funding Information: This work was supported by National Institutes of Health (NIH, United States) grants R01 GM58822 (to W.A.v.d.D.) and R01 GM079038 (to S.K.N.). C.V.G.d.G. was supported by an NIH Chemistry-Biology Interface training program (5T32-GM070421). D.F. was a recipient of a Uehara Memorial Foundation postdoctoral fellowship and a Grant for Studying Overseas from The Naito Foundation, Japan. We thank Keith Brister and colleagues for facilitating diffraction data collection at the Life Sciences Collaborative Access Team (LS-CAT) at Argonne National Lab, Argonne, IL. A Bruker UltrafleXtreme MALDI ToF/ToF mass spectrometer was purchased in part with a grant from the National Institutes of Health (United States, grant S10 RR027109 A). Conceptualization, S.K.N. and W.A.v.d.D.; methodology, D.F. C.V.G.d.G. S.B. Y.H. H.W. N.G. T.L. S.K.N. and W.A.v.d.D.; investigation, D.F. C.V.G.d.G. S.B. Y.H. H.W. N.G. and T.L.; writing ? original draft, D.F. S.K.N. and W.A.v.d.D.; writing ? review & editing, D.F. S.K.N. and W.A.v.d.D.; visualization, D.F. S.K.N. and W.A.v.d.D.; funding acquisition, D.F. C.G.d.G. S.K.N. and W.A.v.d.D.; supervision, S.K.N. and W.A.v.d.D. The authors declare no competing interests. Funding Information: This work was supported by National Institutes of Health (NIH, United States) grants R01 GM58822 (to W.A.v.d.D.) and R01 GM079038 (to S.K.N.). C.V.G.d.G. was supported by an NIH Chemistry-Biology Interface training program ( 5T32-GM070421 ). D.F. was a recipient of a Uehara Memorial Foundatio n postdoctoral fellowship and a Grant for Studying Overseas from The Naito Foundation, Japan. We thank Keith Brister and colleagues for facilitating diffraction data collection at the Life Sciences Collaborative Access Team (LS-CAT) at Argonne National Lab, Argonne, IL. A Bruker UltrafleXtreme MALDI ToF/ToF mass spectrometer was purchased in part with a grant from the National Institutes of Health (United States, grant S10 RR027109 A ). Publisher Copyright: {\textcopyright} 2021 Elsevier Ltd",
year = "2021",
month = dec,
day = "16",
doi = "10.1016/j.chembiol.2021.06.009",
language = "English (US)",
volume = "28",
pages = "1740--1749.e6",
journal = "Cell chemical biology",
issn = "2451-9448",
publisher = "Elsevier Inc.",
number = "12",
}