Three-dimensional structures of the Mn and Mg dTDP complexes of the family GT-2 glycosyltransferase SpsA: a comparison with related NDP-sugar glycosyltransferases.

The vast majority of glycosidic-bond synthesis in nature is performed by glycosyltransferases, which use activated glycosides as the sugar donor. Typically, the activated leaving group is a nucleoside phosphate, lipid phosphate or phosphate. The nucleotide-sugar-dependent glycosyltransferases fall into over 50 sequence-based families, with the largest and most widespread family of inverting transferases named family GT-2. Here, we present the three-dimensional crystal structure of SpsA, the first and currently the only structural representative from family GT-2, in complex with both Mn-dTDP and Mg-dTDP at a resolution of 2 A. These structures reveal how SpsA and related enzymes may display nucleotide plasticity and permit a comparison of the catalytic centre of this enzyme with those from related sequence families whose three-dimensional structures have recently been determined. Family GT-2 enzymes, together with enzymes from families 7, 13 and 43, appear to form a clan of related structures with identical catalytic apparatus and reaction mechanism.

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