Structural Snapshots and Loop Dynamics along the Catalytic Cycle of Glycosyltransferase GpgS

Glycosyltransferases (GTs) play a central role in nature. They catalyze the transfer of a sugar moiety to a broad range of acceptor substrates. GTs are highly selective enzymes, allowing the recognition of subtle structural differences in the sequences and stereochemistry of their sugar and acceptor...

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Detalles Bibliográficos
Autores: Albesa-Jové, David, Romero-García, Javier, Sancho-Vaello, Enea, Contreras, F. Xabier, Rodrigo-Unzueta, Ane, Comino, Natalia, Carreras-González, Ana, Arrasate, Pedro, Urresti, Saioa, Biarnés, Xevi, Planas, Antoni, Guerin, Marcelo E.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/417970
Acceso en línea:http://hdl.handle.net/10261/417970
https://api.elsevier.com/content/abstract/scopus_id/85020708114
Access Level:acceso abierto
Palabra clave:Mycobacteria
Carbohydrate biosynthesis
Carbohydrate modifying enzymes
Enzyme catalysis
Enzyme dynamics
Enzyme mechanism
Enzyme structure
Glycosyltransferases
Lipopolysaccharide
Descripción
Sumario:Glycosyltransferases (GTs) play a central role in nature. They catalyze the transfer of a sugar moiety to a broad range of acceptor substrates. GTs are highly selective enzymes, allowing the recognition of subtle structural differences in the sequences and stereochemistry of their sugar and acceptor substrates. We report here a series of structural snapshots of the reaction center of the retaining glucosyl-3-phosphoglycerate synthase (GpgS). During this sequence of events, we visualize how the enzyme guides the substrates into the reaction center where the glycosyl transfer reaction takes place, and unveil the mechanism of product release, involving multiple conformational changes not only in the substrates/products but also in the enzyme. The structural data are further complemented by metadynamics free-energy calculations, revealing how the equilibrium of loop conformations is modulated along these itineraries. The information reported here represent an important contribution for the understanding of GT enzymes at the molecular level.