Structure of the polyisoprenyl-phosphate glycosyltransferase GtrB and insights into the mechanism of catalysis.


The attachment of a sugar to a hydrophobic polyisoprenyl carrier is the first step for all extracellular glycosylation processes. The enzymes that perform these reactions, polyisoprenyl-glycosyltransferases (PI-GTs) include dolichol phosphate mannose synthase (DPMS), which generates the mannose donor for glycosylation in the endoplasmic reticulum. Here we report the 3.0 Å resolution crystal structure of GtrB, a glucose-specific PI-GT from Synechocystis, showing a tetramer in which each protomer contributes two helices to a membrane-spanning bundle. The active site is 15 Å from the membrane, raising the question of how water-soluble and membrane-embedded substrates are brought into apposition for catalysis. A conserved juxtamembrane domain harbours disease mutations, which compromised activity in GtrB in vitro and in human DPM1 tested in zebrafish. We hypothesize a role of this domain in shielding the polyisoprenyl-phosphate for transport to the active site. Our results reveal the basis of PI-GT function, and provide a potential molecular explanation for DPM1-related disease.





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Publication Info

Ardiccioni, Chiara, Oliver B Clarke, David Tomasek, Habon A Issa, Desiree C von Alpen, Heather L Pond, Surajit Banerjee, Kanagalaghatta R Rajashankar, et al. (2016). Structure of the polyisoprenyl-phosphate glycosyltransferase GtrB and insights into the mechanism of catalysis. Nat Commun, 7. p. 10175. 10.1038/ncomms10175 Retrieved from

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Ziqiang Guan

Research Professor in Biochemistry

We develop and apply mass spectrometry techniques to address biochemical and biomedical questions that are lipid-related. Research projects include:

1) Structural lipidomics

o   Develop and apply high resolution tandem mass spectrometry-based lipidomics for the discovery, structural elucidation and functional study of novel lipids.

2) Elucidation of novel pathways/enzymes of lipid biosynthesis and metabolism

o   Genetic, biochemical and MS approaches are employed to identify the substrates and pathways involved in lipid biosynthesis and metabolism

3) Identification of lipid biomarkers of genetic diseases and cancers

o    Provide molecular insights into the disease mechanisms, as well as to serve as the diagnostic and prognostic tools of diseases.

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