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Updated: Jul 29, 2026

EPR Monitored Redox Titration of the Cofactors of Saccharomyces cerevisiae Nar1
Published on: November 26, 2014
From NAD+ to Nickel Pincer Complex: A Significant Cofactor Evolution Presented by Lactate Racemase
1Key Laboratory of Cluster Science of the Ministry of Education, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 100081, P.R. China.
Abstract:
Lactate racemase (LarA), a new nickel enzyme discovered recently, catalyzes the racemization between d- and l-lactates with a novel nickel pincer cofactor (Ni-PTTMN) derived from nicotinic acid. In this study, by using DFT and a 200-atom active-site model, LarA is revealed to employ a modified proton-coupled hydride-transfer mechanism in which a hydride is transferred to a cofactor pyridine carbon from the substrate α-carbon along with proton transfer from the substrate hydroxy group to a histidine, and then moved back from the opposite side. Tyr294 and Lys298 provide significant acceleration effects by orientating substrates and stabilizing the negative charge developing at the substrate hydroxy oxygen. The barrier was determined to be 12.0 kcal mol-1 , which reveals enhanced racemase activity relative to the LarA reaction using NAD+ -like cofactors. Compared with NAD+ , Ni-PTTMN has a stronger hydride-addition reactivity in moderate and high environmental polarity and may fit perfectly the moderately polar active site of LarA.
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