QM/MM studies reveal how substrate-substrate and enzyme-substrate interactions modulate retaining glycosyltransferases catalysis and mechanism

Hansel Gómez, Fernanda Mendoza, José M. Lluch, Laura Masgrau

Resultado de la investigación: Contribución a los tipos de informe/libroContribución a la conferenciarevisión exhaustiva

10 Citas (Scopus)

Resumen

Glycosyltransferases (GTs) catalyze the biosynthesis of glycosidic linkages by transferring a monosaccharide from a nucleotide sugar donor to an acceptor substrate, and they do that with exquisite regio- and stereospecificity. Retaining GTs act with retention of the configuration at the anomeric carbon of the transferred sugar. Their chemical mechanism has been under debate for long as conclusive experimental data to confirm the mechanism have been elusive. In the past years, quantum mechanical/molecular mechanical (QM/MM) calculations have shed light on the mechanistic discussion. Here, we review the work carried out in our group investigating three of these retaining enzymes (LgtC, α3GalT, and GalNAc-T2). Our results support the controversial front-side attack mechanism as the general mechanism for most retaining GTs. The latest structural data are in agreement with these findings. QM/MM calculations have revealed how enzyme-substrate and substrate-substrate interactions modulate the transfer reaction catalyzed by these enzymes. Moreover, they provide an explanation on why in some cases a strong nucleophilic residue is found on the β-face of the sugar, opening the door to a shift toward a double-displacement mechanism.

Idioma originalInglés
Título de la publicación alojadaAdvances in Protein Chemistry and Structural Biology - Combined Quantum Mechanical and Molecular Mechanical Modelling of Biomolecular Interactions, 2015
EditoresTatyana Karabencheva-Christova
EditorialAcademic Press Inc.
Páginas225-254
Número de páginas30
ISBN (versión impresa)9780128020036
DOI
EstadoPublicada - 1 ene 2015
Publicado de forma externa

Serie de la publicación

NombreAdvances in Protein Chemistry and Structural Biology
Volumen100
ISSN (versión impresa)1876-1623

Áreas temáticas de ASJC Scopus

  • Biología estructural
  • Bioquímica

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