The Department of Biochemistry's weekly BCH 252 seminar series is presented this week by
Dr. Robert P. Hausinger, Michigan State University
Seminar Title:“Biosynthesis and Function of the Nickel-Pincer Nucleotide Cofactor”
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.
Seminar Host: Dr. Linlin Zhao; firstname.lastname@example.org