Journal Article10.1146/ANNUREV.BIOCHEM.76.061005.092322
Glycosyltransferases: structures, functions, and mechanisms.
1.9K
TL;DR: The expected two-step double-displacement mechanism is rendered less likely by the lack of conserved architecture in the region where a catalytic nucleophile would be expected, and a mechanism involving a short-lived oxocarbenium ion intermediate now seems the most likely, with the leaving phosphate serving as the base.
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Abstract: Glycosyltransferases catalyze glycosidic bond formation using sugar donors containing a nucleoside phosphate or a lipid phosphate leaving group. Only two structural folds, GT-A and GT-B, have been identified for the nucleotide sugar-dependent enzymes, but other folds are now appearing for the soluble domains of lipid phosphosugar-dependent glycosyl transferases. Structural and kinetic studies have provided new insights. Inverting glycosyltransferases utilize a direct displacement S(N)2-like mechanism involving an enzymatic base catalyst. Leaving group departure in GT-A fold enzymes is typically facilitated via a coordinated divalent cation, whereas GT-B fold enzymes instead use positively charged side chains and/or hydroxyls and helix dipoles. The mechanism of retaining glycosyltransferases is less clear. The expected two-step double-displacement mechanism is rendered less likely by the lack of conserved architecture in the region where a catalytic nucleophile would be expected. A mechanism involving a short-lived oxocarbenium ion intermediate now seems the most likely, with the leaving phosphate serving as the base.
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Citations
A practical glycosyltransferase assay for the identification of new inhibitor chemotypes
TL;DR: An operationally simple assay protocol for the identification and evaluation of small molecular glycosyltransferase inhibitors that is robust and inexpensive, requires only short incubation times, and can be carried out in a microplate format, which makes it ideal for high-throughput screening (HTS) campaigns.
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TL;DR: A combination of genome mining and heterologous expression techniques is used to identify four novel glycosyltransferase-methyltransferase (GT-MT) functional modules from Hypocreales fungi, providing a set of efficient biocatalysts for the combinatorial biosynthesis of small molecule glycosides that may have significant importance to pharmaceutical, agricultural, and food industries.
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Uncovering a glycosyltransferase provides insights into the glycosylation step during macrolactin and bacillaene biosynthesis
TL;DR: The identification of a glycosyltransferase (GT) gene bmmGT1, which is located at different locus from the MLN gene cluster in the genome of marine‐derived Bacillus marinus B‐9987, and its functional characterization as an MLN GT, thus affording five novel MLNs analogues are reported.
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Mechanistic study of CMP-Neu5Ac hydrolysis by α2,3-sialyltransferase from Pasteurella dagmatis.
Katharina Schmölzer,Christiane Luley-Goedl,Tibor Czabany,Doris Ribitsch,Helmut Schwab,Hansjörg Weber,Bernd Nidetzky +6 more
TL;DR: Using in situ proton NMR, it is shown that hydrolysis of CMP‐Neu5Ac by Pasteurella dagmatis α2,3‐sialyltransferase (PdST) occurs with axial‐to‐equatorial inversion of the configuration at the anomeric center to release the α‐Nei5Ac product, and a catalytic mechanism is proposed where water replaces the sugar substrate as a sialyl group acceptor.
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