6tkv
From Proteopedia
Crystal structure of the human FUT8 in complex with GDP and a biantennary complex N-glycan
Structural highlights
FunctionFUT8_HUMAN Catalyzes the addition of fucose in alpha 1-6 linkage to the first GlcNAc residue, next to the peptide chains in N-glycans.[1] Publication Abstract from PubMedCore-fucosylation is an essential biological modification by which a fucose is transferred from GDP-beta-L-fucose to the innermost N-acetylglucosamine residue of N-linked glycans. A single human enzyme alpha1,6-fucosyltransferase (FUT8) is the only enzyme responsible for this modification via the addition of an alpha-1,6-linked fucose to N-glycans. To date, the details of substrate recognition and catalysis by FUT8 remain unknown. Here, we report the crystal structure of FUT8 complexed with GDP and a biantennary complex N-glycan (G0), which provides insight into both substrate recognition and catalysis. FUT8 follows an SN2 mechanism and deploys a series of loops and an alpha-helix which all contribute in forming the binding site. An exosite, formed by one of these loops and an SH3 domain, is responsible for the recognition of branched sugars, making contacts specifically to the alpha1,3 arm GlcNAc, a feature required for catalysis. This information serves as a framework for inhibitor design, and helps to assess its potential as a therapeutic target. Structural basis for substrate specificity and catalysis of alpha1,6-fucosyltransferase.,Garcia-Garcia A, Ceballos-Laita L, Serna S, Artschwager R, Reichardt NC, Corzana F, Hurtado-Guerrero R Nat Commun. 2020 Feb 20;11(1):973. doi: 10.1038/s41467-020-14794-z. PMID:32080177[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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