Evolutionary mystery revealed by structures of a key enzyme in the synthesis of glycolipids

Cells produce hundreds of different sugar-bearing lipids called glycosphingolipids. The synthesis of almost all of them traces back to a single enzyme: UDP-glucose ceramide glucosyltransferase (UGCG), which catalyses a key early step in the glycosphingolipid biosynthetic pathway. How this gatekeeper enzyme works at the molecular level has been unclear for decades. Writing in Nature, Wu et al.1 present eight structures of UGCG in various functional states, which reveal an unforeseen catalytic mechanism, information about how therapeutic drugs inhibit the enzyme and a ‘brake’ feature found only in primate UGCGs.

doi: https://doi.org/10.1038/d41586-026-02378-8

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Competing Interests The authors declare no competing interests.

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