Human fucosyltransferase (FUT)

Human fucosyltransferases (FUTs) are a family of enzymes responsible for the transfer of L-fucose from the donor substrate GDP-fucose to various acceptor molecules, including glycoproteins and glycolipids (UniProt: P40855). This family consists of several members (FUT1-FUT11 and POFUT1-2) that are classified based on the specific linkage they create, such as alpha-1,2, alpha-1,3/4, or alpha-1,6 (PubMed: 30261246). These enzymes play a pivotal role in the synthesis of ABO blood group antigens and Lewis antigens, which are critical for cell-cell recognition and the recruitment of leukocytes to sites of inflammation. In many cancers, the overexpression of specific FUTs, such as FUT8, leads to increased core fucosylation of receptors like TGF-beta and EGF, promoting tumor growth, epithelial-mesenchymal transition, and metastasis (PubMed: 28651078). Additionally, the production of sialyl Lewis X (sLeX) by FUT3, FUT4, and FUT7 facilitates the adhesion of circulating tumor cells to the vascular endothelium. Therapeutic targeting of FUTs is an active area of research, with small-molecule inhibitors like 2-fluorofucose being investigated for their ability to reduce pathological fucosylation and enhance the efficacy of other treatments (PubMed: 23934104). Furthermore, the modulation of FUT8 activity is a cornerstone of glycoengineering in the production of therapeutic antibodies to enhance their immune-mediated killing capacity (PubMed: 23014483).

Other names

Alpha-fucosyltransferaseFucTGDP-L-fucose:beta-D-galactoside 2-alpha-L-fucosyltransferaseGlycosyltransferase family 10

Fucosyltransferase inhibitors typically act as substrate mimetics or metabolic decoys that compete with GDP-fucose or the glycan acceptor, thereby blocking the enzymatic addition of fucose to glycoproteins and glycolipids (PubMed: 23934104).