元动力学
基质(水族馆)
糖基
化学
糖基转移酶
底物特异性
电子转移
酶
立体化学
分子动力学
计算化学
生物化学
生物
光化学
生态学
作者
Erandi Lira‐Navarrete,Javier Iglesias‐Fernández,Wesley F. Zandberg,Ismael Compañón,Yun Kong,Francisco Corzana,Bernardine M. Pinto,Henrik Clausen,Jesús M. Peregrina,David J. Vocadlo,Carme Rovira,Ramón Hurtado‐Guerrero
标识
DOI:10.1002/anie.201402781
摘要
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 atomic-electronic 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 SN i-type reaction in which the substrate N-acetyl sugar substituent coordinates efficient glycosyl transfer.
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