A structural view of nickel-pincer nucleotide cofactor-related biochemistry.

The nickel-pincer nucleotide (NPN) is an organometallic cofactor that was first discovered in lactate racemase from Lactiplantibacillus plantarum. In this review, we provide an overview on the structure-function relationships of enzymes that utilize or are involved in the biosynthesis of the NPN cofactor. Recent structural advances have greatly extended our understanding of the biological role of the NPN cofactor in a diverse family of 2-hydroxyacid racemases and epimerases. Moreover, structural studies of the accessory proteins LarB (a combined carboxylase/hydrolase), two distinct forms of LarE (an ATP-dependent sulfur transferase), and LarC (a CTP-dependent nickel insertase) have elucidated key features in the biosynthetic pathway for the NPN cofactor. Finally, we discuss the potential of future structural investigations to uncover additional enzymes that synthesize and use the NPN cofactor to catalyze new reactions.