Structural Characterization and Ligand-Induced Conformational Changes of SenB, a Se-Glycosyltransferase Involved in Selenoneine Biosynthesis

• Type of Material: Article
• Authors: Kendra Ireland, Emory University; Chase M. Kayrouz, Princeton University; Jonathan Huang, Princeton University; Mohammad R. Seyedsayamdost, Princeton University; Katherine M. Davis, Emory University
• Language: English
• Date: 2023-11-15
• Publisher: Biochemistry
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Authors
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.1021/acs.biochem.3c00452
• Title of Journal or Parent Work: American Chemical Society
• Volume: 62
• Issue: 23
• Start Page: 3337
• End Page: 3342
• Grant/Funding Information: The authors thank the National Science Foundation GRFP (1937971 to K.A.I.), the Eli Lilly-Edward C. Taylor Fellowship in Chemistry (to C.M.K.), the Life Sciences Research Foundation Postdoctoral Fellowship sponsored by the Open Philanthropy Project (to J.H.), and the National Institutes of Health (NIH) (Grants R35 GM147557 to K.M.D. and R01 GM129496 to M.R.S.) for financial support.; This research used resources of the Advanced Photon Source, a U.S. Department of Energy Office of Science User Facility operated by Argonne National Laboratory under Contract DE-AC02-06CH11357. GM/CA@APS is funded by the National Cancer Institute (ACB-12002) and the National Institute of General Medical Sciences (NIGMS) (AGM-12006 and P30GM138396), with the Eiger 16M detector funded by NIH Grant S10 OD012289. BioCAT was supported by Grant P30 GM138395, and use of the Pilatus3 × 1M detector was provided by Grant 1S10OD018090, both from NIGMS.
• Keywords: SenB; biosynthetic enzymes; X-ray crystal structure; Selenium
• Research Categories: Chemistry, Biochemistry; Chemistry, Inorganic; Biology, Molecular

Abstract

Selenium (Se) is an essential micronutrient that is found naturally in proteins, nucleic acids, and natural products. Unlike selenoproteins and selenonucleic acids, little is known about the structures of biosynthetic enzymes that incorporate Se into small molecules. Here, we report the X-ray crystal structure of SenB, the first known Se-glycosyltransferase that was recently found to be involved in the biosynthesis of the Se-containing metabolite selenoneine. SenB catalyzes C–Se bond formation using selenophosphate and an activated uridine diphosphate sugar as a Se and glycosyl donor, respectively, making it the first known selenosugar synthase and one of only four bona fide C–Se bond-forming enzymes discovered to date. Our crystal structure, determined to 2.25 Å resolution, reveals that SenB is a type B glycosyltransferase, displaying the prototypical fold with two globular Rossmann-like domains and a catalytic interdomain cleft. By employing complementary structural biology techniques, we find that SenB undergoes both local and global substrate-induced conformational changes, demonstrating a significant increase in α-helicity and a transition to a more compact conformation. Our results provide the first structure of SenB and set the stage for further biochemical characterization in the future.