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A bifunctional O-antigen polymerase structure reveals a new glycosyltransferase family

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Title: A bifunctional O-antigen polymerase structure reveals a new glycosyltransferase family
Author: Clarke, Bradley; Ovchinnikova, Olga; Sweeney, Ryan; Kamski-Hennekam, Evelyn; Gitalis, Russel; Mallette, Evan; Kelly, Steven; Lowary, Todd; Kimber, Matthew; Whitfield, Chris
Department: Department of Molecular and Cellular Biology
Abstract: Lipopolysaccharide O-antigen is an attractive candidate for immunotherapeutic strategies targeting antibiotic-resistant Klebsiella pneumoniae. Several K. pneumoniae O-serotypes are based on a shared O2a-antigen backbone repeating unit; [→3)-α-Galp-(1→3)-β-Galf-(1→]. O2a antigen is synthesized on undecaprenol diphosphate in a pathway involving the O2a polymerase, WbbM, prior to its export by an ABC transporter. This dual domain polymerase possesses a C-terminal galactopyranosyltransferase resembling known GT8 family enzymes, and an N-terminal DUF4422 domain identified here as a galactofuranosyltransferase defining a previously unrecognized family (GT111). Functional assignment of DUF4422 explains how galactofuranose is incorporated into various polysaccharides of importance in vaccine production and the food industry. In the 2.1 Å-resolution structure, three WbbM protomers associate to form a flattened triangular prism connected to a central stalk that orients the active sites towards the membrane. The biochemical, structural and topological properties of WbbM offer broader insight into the mechanisms of assembly of bacterial cell-surface glycans.
Description: This is a post-peer-review, pre-copy edit version of an article published in Nature Chemical Biology. The final authenticated version is available online at: The following terms of use apply:
Date: 2020
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Related Publications: Clarke, B.R., Ovichinnikova, O.G., Sweeny, R.P., Kamski-Hennekan, E.R., Gitalis, R., Mallette, E., Kelly, S.D., Lowary, T.L., Kimber, M.S., and Whitfield, C. (2020) A bifunctional O-antigen polymerase structure reveals a new glycosyltransferase family. Nature Chemical Biology 16:450-457 doi: 10.1038/s41589-020-0494-0

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