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8d0q
From Proteopedia
Human FUT9 bound to GDP-CF3-Fucose and H-Type 2
Structural highlights
FunctionFUT9_HUMAN Catalyzes the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the N-acetyl glucosamine (GlcNAc) of a distal lactosamine unit of a glycoprotein or a glycolipid-linked polylactosamine chains through an alpha-1,3 glycosidic linkage and participates in particular to the Lewis x (Lex)/CD15 epitope biosynthesis in neurons which allows cell differentiation, cell adhesion, and initiation of neurite outgrowth (PubMed:23263199, PubMed:23192350, PubMed:10386598, PubMed:17335083, PubMed:23000574, PubMed:11278338, PubMed:10622713, PubMed:18395013, PubMed:12107078, PubMed:16282604, PubMed:29593094). Also fucosylates di-, tri- and tetraantennary N-glycans linked to glycoproteins and the inner lactosamine unit of the alpha2,3-sialylated polylactosamine resulting in sLex (CD15s) epitope synthesis (PubMed:12107078, PubMed:18395013). Furthermore, it is capable of synthesizing Lewis a (Lea), although to a lesser extent than Lex and Lewis y (Ley) and to confer SELE-dependent, but not SELL- and SELP-selectin-dependent, cell rolling and adhesion by enhancing Lex and sLex synthesis (PubMed:18395013, PubMed:23192350). May also fucosylate the internal LacNAc unit of the polylactosamine chain to form VIM-2 antigen that serves as recognition epitope for SELE.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] Publication Abstract from PubMedMammalian 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 alpha1,3/4-fucosyltransferases (CAZy GT10 family). At present, the only available crystallographic structure of a GT10 member is that of the Helicobacter pylori alpha1,3-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 alpha1,3-fucosyltransferase that generates Lewis(x) and Lewis(y) 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. Structural basis for Lewis antigen synthesis by the alpha1,3-fucosyltransferase FUT9.,Kadirvelraj R, Boruah BM, Wang S, Chapla D, Huang C, Ramiah A, Hudson KL, Prudden AR, Boons GJ, Withers SG, Wood ZA, Moremen KW Nat Chem Biol. 2023 May 18. doi: 10.1038/s41589-023-01345-y. PMID:37202521[11] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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