We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Substrate-Guided Front-Face Reaction Revealed by Combined Structural Snapshots and Metadynamics for the Polypeptide N-Acetylgalactosaminyltransferase 2.
- Authors
Lira ‐ Navarrete, Erandi; Iglesias ‐ Fernández, Javier; Zandberg, Wesley F.; Compañón, Ismael; Kong, Yun; Corzana, Francisco; Pinto, B. Mario; Clausen, Henrik; Peregrina, Jesús M.; Vocadlo, David J.; Rovira, Carme; Hurtado ‐ Guerrero, Ramon
- Abstract
The retaining glycosyltransferase GalNAc-T2 is a member of a large family of human polypeptide GalNAc-transferases 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 and enforce a front-face SNi-type reaction in which the substrate Nacetyl sugar substituent coordinates efficient glycosyl transfer.
- Subjects
N-acetylgalactosaminyltransferase; BIOCHEMICAL substrates; POLYPEPTIDES; CHEMICAL kinetics; QUANTUM mechanics; POST-translational modification; THREONINE; SERINE
- Publication
Angewandte Chemie, 2014, Vol 126, Issue 31, p8345
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201402781