Mechanism of a cytosolic O-glycosyltransferase essential for the synthesis of a bacterial adhesion protein

Chen, Yu; Seepersaud, Ravin; Bensing, Barbara A.; Sullam, Paul M.; Rapoport, Tom A.

doi:10.1073/pnas.1600494113

Title: Mechanism of a cytosolic O-glycosyltransferase essential for the synthesis of a bacterial adhesion protein

Journal Article · Tue Feb 16 00:00:00 EST 2016 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1600494113· OSTI ID:1241075

Chen, Yu ^[1]; Seepersaud, Ravin ^[2]; Bensing, Barbara A. ^[2]; Sullam, Paul M. ^[2]; Rapoport, Tom A. ^[1]

Harvard Medical School, Boston, MA (United States)
San Francisco Veteran Affairs Medical Center, San Francisco, CA (United States); Univ. of California, San Francisco, CA (United States)

O-glycosylation of Ser and Thr residues is an important process in all organisms, which is only poorly understood. Such modification is required for the export and function of adhesin proteins that mediate the attachment of pathogenic Gram-positive bacteria to host cells. Here, we have analyzed the mechanism by which the cytosolic O-glycosyltransferase GtfA/B of Streptococcus gordonii modifies the Ser/Thr-rich repeats of adhesin. The enzyme is a tetramer containing two molecules each of GtfA and GtfB. The two subunits have the same fold, but only GtfA contains an active site, whereas GtfB provides the primary binding site for adhesin. During a first phase of glycosylation, the conformation of GtfB is restrained by GtfA to bind substrate with unmodified Ser/Thr residues. In a slow second phase, GtfB recognizes residues that are already modified with N-acetylglucosamine, likely by converting into a relaxed conformation in which one interface with GtfA is broken. Here, these results explain how the glycosyltransferase modifies a progressively changing substrate molecule.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division; National Institutes of Health (NIH)

Grant/Contract Number:: AC02-06CH11357; GM103403; GM052586; R01-AI041513; R01-AI106987

OSTI ID:: 1241075

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, Issue 9; ISSN 0027-8424

Publisher:: National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 29 works

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