Stanford Advisors

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  • Academic
    arriaza@stanford.edu
    University - Scholar Department: Chemistry Position: Postdoctoral Scholar

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  • Structural and functional studies reveal the molecular basis of substrate promiscuity of a glycosyltransferase originating from a major agricultural pest. The Journal of biological chemistry Arriaza, R. H., Abiskaroon, B., Patel, M., Daneshian, L., Kluza, A., Snoeck, S., Watkins, M. B., Hopkins, J. B., Van Leeuwen, T., Grbic, M., Grbic, V., Borowski, T., Chruszcz, M. 2023; 299 (12): 105421

    Abstract

    The two-spotted spider mite, Tetranychus urticae, is a major cosmopolitan pest that feeds on more than 1100 plant species. Its genome contains an unprecedentedly large number of genes involved in detoxifying and transporting xenobiotics, including 80 genes that code for UDP glycosyltransferases (UGTs). These enzymes were acquired via horizontal gene transfer from bacteria after loss in the Chelicerata lineage. UGTs are well-known for their role in phase II metabolism; however, their contribution to host adaptation and acaricide resistance in arthropods, such as T.urticae, is not yet resolved. TuUGT202A2 (Tetur22g00270) has been linked to the ability of this pest to adapt to tomato plants. Moreover, it was shown that this enzyme can glycosylate a wide range of flavonoids. To understand this relationship at the molecular level, structural, functional, and computational studies were performed. Structural studies provided specific snapshots of the enzyme in different catalytically relevant stages. The crystal structure of TuUGT202A2 in complex with UDP-glucose was obtained and site-directed mutagenesis paired with molecular dynamic simulations revealed a novel lid-like mechanism involved in the binding of the activated sugar donor. Two additional TuUGT202A2 crystal complexes, UDP-(S)-naringenin and UDP-naringin, demonstrated that this enzyme has a highly plastic and open-ended acceptor-binding site. Overall, this work reveals the molecular basis of substrate promiscuity of TuUGT202A2 and provides novel insights into the structural mechanism of UGTs catalysis.

    View details for DOI 10.1016/j.jbc.2023.105421

    View details for PubMedID 37923139

https://orcid.org/0000-0002-8080-1179