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Dr. Marcelo Guerin - Structural basis of glycosyl transfer reactions

Marcelo Guerin

IIS-BioCruces, The Basque Country, Spain

Structural basis of glycosyl transfer reactions

Marcelo will discuss the contribution of his group in investigating the structural and mechanistic properties of enzymes involved in glycosyl transfer reactions. First, he will be focused in the ADP-Glc pyrophosphorylase (AGPase), the enzyme that catalyzes the biosynthesis of the nucleotide sugar ADP-Glc. AGPase, is considered the main regulatory step in glycogen and starch production in bacteria and plants. He will discuss X-ray and CryoEM structures of a homotetrameric AGPase in complex with its physiological positive and negative allosteric regulators, fructose-1,6-bisphosphate (FBP) and AMP. They propose a model in which the energy reporters regulate AGPase catalytic activity by intraprotomer interactions and inter-protomer crosstalk, with a sensory motif and two regulatory loops playing a prominent role. Secondly, they provided for the first time the atomic coordinates of a native Michaelis complex for a glycosyltransferase in the absence of any substrate derivative or protein mutant. Moreover, through a series of unique structural snapshots of the mycobacterial glycosyltransferase GpgS, they visualized how the enzyme guides the substrates into the reaction center and unveiled the mechanism of product release, involving multiple conformational changes not only in the substrates/products but also in the enzyme.

Selected references

  • Cifuente JO, Comino N, Trastoy B, D'Angelo C, Guerin ME. Structural basis of glycogen metabolism in bacteria. Biochem J. 2019 476(14):2059-2092
  • Kalscheuer R, Palacios A, Anso I, Cifuente J, Anguita J, Jacobs WR Jr, Guerin ME, Prados-Rosales R. The Mycobacterium tuberculosis capsule: a cell structure with key implications in pathogenesis. Biochem J. 2019 476(14):1995-2016
  • Cifuente JO, Comino N, D’Angelo C, Marina A, Gil-Carton D, Albesa-Jové D, Guerin ME. The allosteric control mechanism of bacterial glycogen biosynthesis disclosed by cryoEM. Curr Res Struct Biol. 2020 2:89-103
  • Albesa-Jové D, Romero-García J, Sancho-Vaello E, Contreras FX, Rodrigo-Unzueta A, Comino N, Carreras-González A, Arrasate P, Urresti S, Biarnés X, Planas A, Guerin ME. Structural snapshots and loop dynamics along the catalytic cycle of glycosyltransferase GpgS. Structure. 2017 25(7):1034-1044.e3
  • Comino N, Cifuente JO, Marina A, Orrantia A, Eguskiza A, Guerin ME. Mechanistic insights into the allosteric regulation of bacterial ADP-glucose pyrophosphorylases. J Biol Chem. 2017 292(15):6255-6268
  • Cifuente JO, Comino N, Madariaga-Marcos J, López-Fernández S, García-Alija M, Agirre J, Albesa-Jové D, Guerin ME. Structural basis of glycogen biosynthesis regulation in bacteria. Structure. 2016 24(9):1613-22
  • Albesa-Jové D, Mendoza F, Rodrigo-Unzueta A, Gomollón-Bel F, Cifuente JO, Urresti S, Comino N, Gómez H, Romero-García J, Lluch JM, Sancho-Vaello E, Biarnés X, Planas A, Merino P, Masgrau L, Guerin ME. A native ternary complex trapped in a crystal reveals the catalytic mechanism of a retaining glycosyltransferase. Angew Chem Int Ed Engl. 2015 54(34):9898-902

Contact: Jérome Nigou (

Link to attend the seminar:

23 Mar

11:00 - 12:00

Online seminar