title: Alternative Mechanistic Strategy for Enzyme Catalysis in a Ni-Dependent Lactate Racemase (LarA): Intermediate Destabilization by the Cofactor.
abstract: 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.
authors.affiliation: Department of Chemistry, South University of Science and Technology of China, Shenzhen, 518055, P. R. China.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, South University of Science and Technology of China, Shenzhen, 518055, P. R. China.
authors.forename: Lung W
authors.identifier: http://orcid.org/0000-0001-9460-7812
authors.initials: LW
authors.lastname: Chung
mesh_terms: D055162:Biocatalysis; D020134:Catalytic Domain; D006639:Histidine / Q000378:metabolism; D006865:Hydrogenation; D048191:Lactiplantibacillus plantarum / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D008958:Models, Molecular; D009532:Nickel / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism; D019998:Racemases and Epimerases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D006639:Histidine; D009532:Nickel; D019289:Pyruvic Acid; D019998:Racemases and Epimerases; C021498:lactate racemase
keywords: density functional calculations; enzyme catalysis; lactate racemase; metalloenzymes; nickel