Alternative Mechanistic Strategy for Enzyme Catalysis in a Ni-Dependent Lactate Racemase (LarA): Intermediate Destabilization by the Cofactor

作者：Zhang, Xiaoyong; Chung, Lung W.^*

来源：Chemistry - A European Journal, 2017, 23(15): 3623-3630.

DOI：10.1002/chem.201604893

• density functional calculations
• enzyme catalysis
• metalloenzymes
• nickel
• lactate racemase

Recently, a lactate racemase was discovered as a new Ni-dependent enzyme with a unique tethered NAD-like cofactor. We report the first computational study aimed at deciphering the previously unclear role of the Ni-tethered cofactor in reactions of the lactate racemase. Our calculations revealed that the cofactor increases the dehydrogenation barriers. The formation of a metastable NADH-like pyruvate intermediate and two nearby histidine bases are proposed as the key factors in the racemization reaction. Such destabilization of intermediates by the cofactor is uncommon in enzymatic catalysis. This result provides new insight into the design of a reactive metal-tethered NADH-like complex for synthetic hydrogenations.

• 出版日期2017-3
• 单位南方科技大学