8WBV | pdb_00008wbv

A precise swaying map for how promiscuous cellobiose-2-epimerase operate bi-reaction.

(2023) Int J Biol Macromol 253: 127093-127093

• PubMed: 37758108 Search on PubMed
• DOI: https://doi.org/10.1016/j.ijbiomac.2023.127093
• Primary Citation of Related Structures:  
  8WBU, 8WBV


• PubMed Abstract: 
  

  Promiscuous enzymes play a crucial role in organism survival and new reaction mining. However, comprehensive mapping of the catalytic and regulatory mechanisms hasn't been well studied due to the characteristic complexity. The cellobiose 2-epimerase from Caldicellulosiruptor saccharolyticus (CsCE) with complex epimerization and isomerization was chosen to comprehensively investigate the promiscuous mechanisms. Here, the catalytic frame of ring-opening, cis-enediol mediated catalysis and ring-closing was firstly determined. To map the full view of promiscuous CE, the structure of CsCE complex with the isomerized product glucopyranosyl-β1,4-fructose was determined. Combined with computational calculation, the promiscuity was proved a precise cooperation of the double subsites, loop rearrangement, and intermediate swaying. The flexible loop was like a gear, whose structural reshaping regulates the sway of the intermediates between the two subsites of H377-H188 and H377-H247, and thus regulates the catalytic directions. The different protonated states of cis-enediol intermediate catalyzed by H188 were the key point for the catalysis. The promiscuous enzyme tends to utilize all elements at hand to carry out the promiscuous functions.

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Organizational Affiliation: 
• Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China; State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, 214122 Wuxi, China.
State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, 214122 Wuxi, China; Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, Wuxi, Jiangsu 214122, China.
Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
Department of Micro/Nano Electronics, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
Okinawa Institute of Science and Technology, Onna, Okinawa 904-0495, Japan; Department of Chemistry, University of California Davis, Davis, CA 95616, United States; Department of Molecular and Cellular Biology, University of California Davis, Davis, CA 95616, United States.
Department of Chemistry, University of California Davis, Davis, CA 95616, United States; Department of Molecular and Cellular Biology, University of California Davis, Davis, CA 95616, United States.
Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China; NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai 200062, China; Department of Chemistry, New York University, New York, NY 10003, United States.
Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China; NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai 200062, China. Electronic address: Ljzhang@chem.ecnu.edu.cn.
State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, 214122 Wuxi, China; Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, Wuxi, Jiangsu 214122, China. Electronic address: yrj@jiangnan.edu.cn.
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