Abstract
Lactate racemase interconverts the L‐ and D‐isomers of lactic acid, a central metabolic intermediate in cells. In 2015, the Hausinger laboratory discovered that the enzyme responsible for this activity in Lactobacillus plantarum, LarA, possesses a covalently‐tethered coenzyme they named the nickel‐pincer nucleotide (NPN) cofactor. This novel organometallic molecule contains a square‐planar nickel atom bound by one histidine residue and tri‐coordinated by a modified pyridinium mononucleotide forming C‐Ni and two S‐Ni bonds. In this seminar, Dr. Hausinger will describe an array of structure/function studies that characterize the three enzymes used for biosynthesis of the NPN cofactor. LarB is a carboxylase/hydrolase of nicotinic acid adenine dinucleotide that forms a dicarboxylated pyridine mononucleotide (P2CMN). LarE is an ATP‐dependent sacrificial sulfur insertase that converts P2CMN into a species with two thiocarboxylic acids (P2TMN). Finally, LarC is a CTP‐dependent nickel insertase or cyclometallase that transforms P2TMN into NPN. The NPN cofactor is incorporated into a variety of 2‐hydroxyacid racemases and selected sugar epimerases where it catalyzes proton‐coupled hydride transfer reactions.
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