3 years ago

Structural Snapshots of α-1,3-Galactosyltransferase with Native Substrates: Insight into the Catalytic Mechanism of Retaining Glycosyltransferases

Structural Snapshots of α-1,3-Galactosyltransferase with Native Substrates: Insight into the Catalytic Mechanism of Retaining Glycosyltransferases
M. Ángela Sainz-Polo, Marcelo E. Guerin, Alberto Marina, David Albesa-Jové
Glycosyltransferases (GTs) are a key family of enzymes that catalyze the synthesis of glycosidic bonds in all living organisms. The reaction involves the transfer of a glycosyl moiety and can proceed with retention or inversion of the anomeric configuration. To date, the catalytic mechanism of retaining GTs is a topic of great controversy, particularly for those enzymes containing a putative nucleophilic residue in the active site, for which the occurrence of a double-displacement mechanism has been suggested. We report native ternary complexes of the retaining glycosyltransferase α-1,3-galactosyltransferase (α3GalT) from Bos taurus, which contains such a nucleophile in the active site, in a productive mode for catalysis in the presence of its sugar donor UDP-Gal, the acceptor substrate lactose, and the divalent cation cofactor. This new experimental evidence supports the occurrence of a front-side substrate-assisted SNi-type reaction for α3GalT, and suggests a conserved common catalytic mechanism among retaining GTs. Crystal clear: A crystal structure was obtained for a native ternary complex of the GT6 family glycosyltransferase α-1,3-galactosyltransferase (α3GalT), which contains a putative nucleophile in the active site, in a productive mode for catalysis. The configuration of the active center supports the occurrence of a front-side substrate-assisted SNi-type reaction, and suggests a conserved common catalytic mechanism among retaining glycosyltransferases.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201707922

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