Resource type
Date created
2014-06-20
Authors/Contributors
Author (aut): Lira‐Navarrete, Erandi
Author (aut): Iglesias‐Fernández, Javier
Author (aut): Zandberg, Wesley F.
Author (aut): Compañón, Ismael
Author (aut): Kong, Yun
Author (aut): Corzana, Francisco
Author (aut): Pinto, B. Mario
Author (aut): Clausen, Henrik
Author (aut): Peregrina, Jesús M.
Author (aut): Vocadlo, David J.
Author (aut): Rovira, Carme
Author (aut): Hurtado‐Guerrero, Ramon
Abstract
The retaining glycosyltransferase GalNAc-T2 is a member of a large family of human polypeptide GalNActransferases that is responsible for the post-translational modification of many cell-surface proteins. By the use of combined structural and computational approaches, we provide the first set of structural snapshots of the enzyme during the catalytic cycle and combine these with quantum-mechanics/molecular-mechanics (QM/MM) metadynamics to unravel the catalytic mechanism of this retaining enzyme at the atomicelectronic level of detail. Our study provides a detailed structural rationale for an ordered bi–bi kinetic mechanism and reveals critical aspects of substrate recognition, which dictate the specificity for acceptor Thr versus Ser residues andenforce a front-face SNi-type reaction in which the substrate Nacetyl sugar substituent coordinates efficient glycosyl transfer.
Document
Identifier
DOI: 10.1002/anie.201402781
Published as
Lira-Navarrete, E., Iglesias-Fernández, J., Zandberg, W. F., Compañón, I., Kong, Y., Corzana, F., Pinto, B. M., Clausen, H., Peregrina, J. M., Vocadlo, D. J., Rovira, C., & Hurtado-Guerrero, R. (2014). Substrate-Guided Front-Face Reaction Revealed by Combined Structural Snapshots and Metadynamics for the Polypeptide N-Acetylgalactosaminyltransferase 2. Angewandte Chemie International Edition, 53(31), 8206–8210. https://doi.org/10.1002/anie.201402781
Publication details
Publication title
Angewandte Chemie International Edition
Document title
Substrate‐Guided Front‐Face Reaction Revealed by Combined Structural Snapshots and Metadynamics for the Polypeptide N‐Acetylgalactosaminyltransferase 2
Date
2014
Volume
53
Issue
31
First page
8206
Last page
8210
Published article URL
Copyright statement
Copyright is held by the author(s).
Scholarly level
Peer reviewed?
Yes
Language
English
Member of collection