2019 is a very special year in chemistry. 2019 marks two major anniversaries: the 100th anniversary of the founding of the International Union of Pure and Applied Chemistry (IUPAC), and the 150th anniversary of Dimitri Mendeleev’s first publication on the Periodic Table of Elements [1]. IUPAC is the global organization that, among many other things, established a common language for chemistry—enabling scientific research, education, and trade. In a similar manner, Mendeleev’s system classified all the elements that were known at the time, and even predicted the existence of elements that would only come to be discovered years later. These two anniversaries are closely entwined, as IUPAC has played a major role developing of the modern Periodic Table by ensuring that the most authoritative version of the table is accessible to everyone [2], establishing names and symbols for the newly discovered elements, and also constantly reviewing its accuracy through the IUPAC Commission on Isotopic Abundances and Atomic Weights.

In 2019, IUPAC introduced the “Top Ten Emerging Technologies in Chemistry” [1].* This initiative commemorated both IUPAC’s 100th anniversary and the International Year of the Periodic Table, a worldwide event that celebrated 150 years since the first publication of Mendeleev’s most famous chemistry icon. Now, IUPAC wants to transform this project into yet another landmark. Every year, the “Top Ten Emerging Technologies in Chemistry” will identify innovations with tremendous potential to change the current chemical and industrial landscape [2].*

Glycosyltransferases (GTs) comprise a prominent family of enzymes that play critical roles in a variety of cellular processes, including cell signaling, cell development, and host-pathogen interactions. Glycosyl transfer can proceed with either inversion or retention of the anomeric configuration with respect to the reaction substrates and products. The elucidation of the catalytic mechanism of retaining GTs remains a major challenge. A native ternary complex of a GT in a productive mode for catalysis is reported, that of the retaining glucosyl-3-phosphoglycerate synthase GpgS from M. tuberculosis in the presence of the sugar donor UDP-Glc, the acceptor substrate phosphoglycerate, and the divalent cation cofactor. Through a combination of structural, chemical, enzymatic, molecular dynamics, and quantum-mechanics/molecular-mechanics (QM/MM) calculations, the catalytic mechanism was unraveled, thereby providing a strong experimental support for a front-side substrate-assisted SN i-type reaction.

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