Dataset Information

Structural basis of substrate recognition and catalysis by fucosyltransferase 8.

ABSTRACT: Fucosylation of the innermost GlcNAc of N-glycans by fucosyltransferase 8 (FUT8) is an important step in the maturation of complex and hybrid N-glycans. This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder. The acceptor substrate preferences of FUT8 are well-characterized and provide a framework for understanding N-glycan maturation in the Golgi; however, the structural basis of these substrate preferences and the mechanism through which catalysis is achieved remain unknown. Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolution. These structures provide insights into a unique conformational change associated with donor substrate binding, common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis. Together with molecular dynamics simulations, the structures also revealed how FUT8 dimerization plays an important role in defining the acceptor substrate-binding site. Collectively, this information significantly builds on our understanding of the core fucosylation process.

SUBMITTER: Jarva MA

PROVIDER: S-EPMC7212660 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Structural basis of substrate recognition and catalysis by fucosyltransferase 8.

Järvå Michael A MA Dramicanin Marija M Lingford James P JP Mao Runyu R John Alan A Jarman Kate E KE Grinter Rhys R Goddard-Borger Ethan D ED

The Journal of biological chemistry 20200327 19

Fucosylation of the innermost GlcNAc of <i>N</i>-glycans by fucosyltransferase 8 (FUT8) is an important step in the maturation of complex and hybrid <i>N</i>-glycans. This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder. The acceptor substrate preferences of FUT8 are well-characterized and ...[more]

PMID: 32220931

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Dataset Information

Structural basis of substrate recognition and catalysis by fucosyltransferase 8.

Publications

Structural basis of substrate recognition and catalysis by fucosyltransferase 8.

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