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Proteins. 2013 Jul;81(7):1277-82. doi: 10.1002/prot.24289. Epub 2013 Apr 20.

Crystal structure of SsfS6, the putative C-glycosyltransferase involved in SF2575 biosynthesis.

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Department of Biochemistry and Cell Biology, Rice University, Houston, Texas 77005, USA.


The molecule known as SF2575 from Streptomyces sp. is a tetracycline polyketide natural product that displays antitumor activity against murine leukemia P388 in vivo. In the SF2575 biosynthetic pathway, SsfS6 has been implicated as the crucial C-glycosyltransferase (C-GT) that forms the C-C glycosidic bond between the sugar and the SF2575 tetracycline-like scaffold. Here, we report the crystal structure of SsfS6 in the free form and in complex with TDP, both at 2.4 Å resolution. The structures reveal SsfS6 to adopt a GT-B fold wherein the TDP and docked putative aglycon are consistent with the overall C-glycosylation reaction. As one of only a few existing structures for C-glycosyltransferases, the structures described herein may serve as a guide to better understand and engineer C-glycosylation.

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