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ChemistryOpen. 2019 Jun 11;8(6):760-769. doi: 10.1002/open.201900116. eCollection 2019 Jun.

Insights into Allosteric Control of Human Blood Group A and B Glycosyltransferases from Dynamic NMR.

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1
Institute of Chemistry and Metabolomics University of Lübeck 23562 Lübeck Germany.

Abstract

Human blood group A and B glycosyltransferases (GTA, GTB) are retaining glycosyltransferases, requiring a catalytic mechanism that conserves the anomeric configuration of the hexopyranose moiety of the donor substrate (UDP-GalNAc, UDP-Gal). Previous studies have shown that GTA and GTB cycle through structurally distinct states during catalysis. Here, we link binding and release of substrates, substrate-analogs, and products to transitions between open, semi-closed, and closed states of the enzymes. Methyl TROSY based titration experiments in combination with zz-exchange experiments uncover dramatic changes of binding kinetics associated with allosteric interactions between donor-type and acceptor-type ligands. Taken together, this highlights how allosteric control of on- and off-rates correlates with conformational changes, driving catalysis to completion.

KEYWORDS:

Methyl TROSY; allosteric effects; binding kinetics; chemical shift perturbation; glycosyltransferase

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