8D0Q

Human FUT9 bound to GDP-CF3-Fucose and H-Type 2

Summary for 8D0Q

• Entry DOI: 10.2210/pdb8d0q/pdb
• Related: 8D0O 8D0P
• Descriptor: 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase 9, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-L-fucopyranose-(1-2)-beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: glycosyltransferase, alpha-(1, 3)-fucosyltransferase, gt 10, gt-b fold, inverting mechanism, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 40614.65

Authors

Kadirvelraj, R.,Wood, Z.A. (deposition date: 2022-05-26, release date: 2023-05-31, Last modification date: 2023-10-25)

Primary citation

Kadirvelraj, R.,Boruah, B.M.,Wang, S.,Chapla, D.,Huang, C.,Ramiah, A.,Hudson, K.L.,Prudden, A.R.,Boons, G.J.,Withers, S.G.,Wood, Z.A.,Moremen, K.W.
Structural basis for Lewis antigen synthesis by the alpha 1,3-fucosyltransferase FUT9.
Nat.Chem.Biol., 19:1022-1030, 2023

PubMed Abstract: Mammalian cell surface and secreted glycoproteins exhibit remarkable glycan structural diversity that contributes to numerous physiological and pathogenic interactions. Terminal glycan structures include Lewis antigens synthesized by a collection of α1,3/4-fucosyltransferases (CAZy GT10 family). At present, the only available crystallographic structure of a GT10 member is that of the Helicobacter pylori α1,3-fucosyltransferase, but mammalian GT10 fucosyltransferases are distinct in sequence and substrate specificity compared with the bacterial enzyme. Here, we determined crystal structures of human FUT9, an α1,3-fucosyltransferase that generates Lewis and Lewis antigens, in complex with GDP, acceptor glycans, and as a FUT9-donor analog-acceptor Michaelis complex. The structures reveal substrate specificity determinants and allow prediction of a catalytic model supported by kinetic analyses of numerous active site mutants. Comparisons with other GT10 fucosyltransferases and GT-B fold glycosyltransferases provide evidence for modular evolution of donor- and acceptor-binding sites and specificity for Lewis antigen synthesis among mammalian GT10 fucosyltransferases.

PubMed: 37202521
DOI: 10.1038/s41589-023-01345-y

Experimental method

X-RAY DIFFRACTION (1.39 Å)