Nickel-pincer nucleotide cofactor

Abstract

A novel organometallic cofactor, nickel pyridinium-3,5-dithiocarboxylic acid mononucleotide, was recently discovered in lactate racemase (LarA) of Lactobacillus plantarum. This review summarizes the substantial progress made in uncovering the function of this cofactor as a transient hydride acceptor in the LarA mechanism. The latest developments related to cofactor biosynthesis reveal insights into a pathway in which LarB serves as a nicotinic acid adenine dinucleotide hydrolase/carboxylase, LarE acts as a sacrificial sulfur transferase, and LarC functions as a nickel insertase, forming the nickel-pincer nucleotide cofactor that becomes covalently tethered to LarA in some bacteria. Bioinformatic studies reveal a widespread occurrence of larA, larB, larC, and larE orthologs in microorganisms, and additional roles for the cofactor are considered.