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Protein flexibility drives sugar rotation and high substrate promiscuity in a GDP-sugar 4-epimerase

2025/01/01 by Carlos Josué Alvarez Quispe, Koen Beerens, A.M.W.H. Thunnissen +3 · 2 voices
Materials Science · Medicine · #Diet, Metabolism, and Disease #Enzyme Structure and Function #Pancreatic function and diabetes

paper · pdf · doi:10.1016/j.csbj.2025.05.037

openalex publication_date 2025/01/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31

Abstract

UDP-galactose 4-epimerases (Gal4Es) catalyze the inversion of the 4-hydroxyl configuration of a sugar moiety from an NDP-sugar through a three-step process: oxidation, rotation and reduction. Despite extensive biochemical and structural studies, the role of protein dynamics on substrate specificity remains poorly understood. The recently identified subgroup of GDP-sugar 4-epimerases, notable for its exceptional substrate promiscuity, provides an intriguing model to investigate the role of dynamics in the Gal4E catalytic mechanism and the unique promiscuity of the subgroup.

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