6TKV

Crystal structure of the human FUT8 in complex with GDP and a biantennary complex N-glycan

Summary for 6TKV

• Entry DOI: 10.2210/pdb6tkv/pdb
• Descriptor: Alpha-(1,6)-fucosyltransferase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, GUANOSINE-5'-DIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: glycosyltransferase, sugar nucleotide, acceptor substrate, catalysis, sugar binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 111371.82

Authors

Garcia-Garcia, A.,Ceballos-Laita, L.,Serna, L.,Artschwager, R.,Reichardt, N.C.,Corzana, F.,Hurtado-Guerrero, R. (deposition date: 2019-11-29, release date: 2020-01-29, Last modification date: 2024-10-16)

Primary citation

Garcia-Garcia, A.,Ceballos-Laita, L.,Serna, S.,Artschwager, R.,Reichardt, N.C.,Corzana, F.,Hurtado-Guerrero, R.
Structural basis for substrate specificity and catalysis of alpha 1,6-fucosyltransferase.
Nat Commun, 11:973-973, 2020

PubMed Abstract: Core-fucosylation is an essential biological modification by which a fucose is transferred from GDP-β-L-fucose to the innermost N-acetylglucosamine residue of N-linked glycans. A single human enzyme α1,6-fucosyltransferase (FUT8) is the only enzyme responsible for this modification via the addition of an α-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 S2 mechanism and deploys a series of loops and an α-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 α1,3 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.

PubMed: 32080177
DOI: 10.1038/s41467-020-14794-z

Experimental method

X-RAY DIFFRACTION (1.95 Å)