| Structural highlights
Function
[GPGS_MYCTU] Involved in the biosynthesis of methylglucose lipopolysaccharides (MGLPs). Catalyzes the condensation of NDP-glucose and 3-phospho-glycerate (3-PGA) to yield glucosyl-3-phosphoglycerate (GPG).[1]
Publication Abstract from PubMed
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.
A Native Ternary Complex Trapped in a Crystal Reveals the Catalytic Mechanism of a Retaining Glycosyltransferase.,Albesa-Jove D, Mendoza F, Rodrigo-Unzueta A, Gomollon-Bel F, Cifuente JO, Urresti S, Comino N, Gomez H, Romero-Garcia J, Lluch JM, Sancho-Vaello E, Biarnes X, Planas A, Merino P, Masgrau L, Guerin ME Angew Chem Int Ed Engl. 2015 Jul 1. doi: 10.1002/anie.201504617. PMID:26136334[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Urresti S, Albesa-Jove D, Schaeffer F, Pham HT, Kaur D, Gest P, van der Woerd MJ, Carreras-Gonzalez A, Lopez-Fernandez S, Alzari PM, Brennan PJ, Jackson M, Guerin ME. Mechanistic insights into the retaining glucosyl-3-phosphoglycerate synthase from mycobacteria. J Biol Chem. 2012 May 25. PMID:22637481 doi:10.1074/jbc.M112.368191
- ↑ Albesa-Jove D, Mendoza F, Rodrigo-Unzueta A, Gomollon-Bel F, Cifuente JO, Urresti S, Comino N, Gomez H, Romero-Garcia J, Lluch JM, Sancho-Vaello E, Biarnes X, Planas A, Merino P, Masgrau L, Guerin ME. A Native Ternary Complex Trapped in a Crystal Reveals the Catalytic Mechanism of a Retaining Glycosyltransferase. Angew Chem Int Ed Engl. 2015 Jul 1. doi: 10.1002/anie.201504617. PMID:26136334 doi:http://dx.doi.org/10.1002/anie.201504617
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