標題: Catalytic Roles of Histidine and Arginine in Pyruvate Class II Aldolase: A Perspective from QM/MM Metadynamics
作者: Huang, Gou-Tao
Yu, Jen-Shiang K.
生物科技學系
生物資訊及系統生物研究所
分子醫學與生物工程研究所
Department of Biological Science and Technology
Institude of Bioinformatics and Systems Biology
Institute of Molecular Medicine and Bioengineering
關鍵字: aldol cleavage;salt bridge;aldolase;pyruvate;QM/MM;metadynamics
公開日期: 1-Dec-2017
摘要: The retro-aldol reaction catalyzed by pyruvate class II aldolase is investigated with QM/MM metadynamics; this enzyme transforms the substrate of 4-hydrox-y-2-ketoacid into pyruvate and aldehyde through the aldol cleavage. The hydroxyl group of the substrate is deprotonated by His45 with the aid of the metal-bound water, while the metal-bound hydroxide proposed in the literature is observed as a transient species. The deprotonation appears to enhance substrate binding between the deprotonated substrate and the active site. The reactive alkoxide is further stabilized by the salt bridge of Arg70-Asp42, facilitating the following aldol cleavage. The simulations show that the C-C bond cleavage is the rate-determining step, and the calculated barrier of approximately 14 kcal mol(-1) agrees reasonably with experimental data.
URI: http://dx.doi.org/10.1021/acscata1.7b03398
http://hdl.handle.net/11536/144191
ISSN: 2155-5435
DOI: 10.1021/acscata1.7b03398
期刊: ACS CATALYSIS
Volume: 7
起始頁: 8130
結束頁: 8133
Appears in Collections:Articles