Structural Snapshots of α‐1, 3‐Galactosyltransferase with Native Substrates: Insight into the Catalytic Mechanism of Retaining Glycosyltransferases. Issue 47 (20th October 2017)

• Record Type: Journal Article
• Authors: Albesa‐Jové, David; Sainz‐Polo, M. Ángela; Marina, Alberto; Guerin, Marcelo E.
• Is Part Of: Angewandte Chemie international edition. Volume 56:Issue 47(2017)
• Page Start: 14853
• Page End: 14857
• Publication Date: 2017-10-20
• Subjects: enzyme catalysis -- enzymes -- glycosyltransferases -- reaction mechanisms -- structural biology; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201707922
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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 SN i‐type reaction for α3GalT, and suggests a conserved common catalytic mechanism among retaining GTs. Abstract : 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 SN i‐type reaction, and suggests a conserved common catalytic mechanism among retaining glycosyltransferases.