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

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Clarke, Bradley
Ovchinnikova, Olga
Sweeney, Ryan
Kamski-Hennekam, Evelyn
Gitalis, Russel
Mallette, Evan
Kelly, Steven
Lowary, Todd
Kimber, Matthew
Whitfield, Chris

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Nature Research


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.


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: https://doi.org/10.1038/s41589-020-0494-0. The following terms of use apply: https://www.springer.com


lipopolysaccharide O-antigen, galactofuranosyltransferase, WbbM, Klebsiella pneumoniae