title: Crystal structure of SsfS6, the putative C-glycosyltransferase involved in SF2575 biosynthesis.
abstract: 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.
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston, Texas 77005, USA.
authors.forename: Fengbin
authors.initials: F
authors.lastname: Wang
authors.forename: Maoquan
authors.initials: M
authors.lastname: Zhou
authors.forename: Shanteri
authors.initials: S
authors.lastname: Singh
authors.forename: Ragothaman M
authors.initials: RM
authors.lastname: Yennamalli
authors.forename: Craig A
authors.initials: CA
authors.lastname: Bingman
authors.forename: Jon S
authors.initials: JS
authors.lastname: Thorson
authors.forename: George N
authors.initials: GN
authors.lastname: Phillips
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001426:Bacterial Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006031:Glycosylation; D016695:Glycosyltransferases / Q000096:biosynthesis / Q000737:chemistry; D007941:Leukemia P388 / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D013302:Streptomyces / Q000737:chemistry / Q000378:metabolism; D013754:Tetracyclines / Q000096:biosynthesis / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D013754:Tetracyclines; C074360:SF 2575; D016695:Glycosyltransferases