Biosynthesis and Functions of the Nickel-Pincer Nucleotide (NPN) Cofactor

Abstract

Biometals webinar presentation and International Biometals SocietyThis short presentation will be an introduction to the Biometals webinars series organized by the International Biometals society and the Biometals Journal.Biometal webinars will be monthly in 2024 jointly organized by the Cassiny platform, Springer and the International Biometals society. It will be with two speakers, one senior scientist one younger. One of them at least author of a recent Biometals article. confirmed senior speakers: January 16th, 2024:Bob Hausinger (Ni) ; February 13th, 2024: David Frazer (Fe) ; March 12th , 2024: Wolfgang Maret (Zn) ; April 9th 2024: Alison Butler (Fe) ; May 7th 2024: John Helmann (Fe) ; Free of access, each webinar will be live and accessible live on the Cassyni Platform followed by questions and answers time. It will also be recorded and be accessible (if accepted by the speaker) on the platform. A DOI number will be assigned to the recorded presentation. This will not replace the face-to-face Biometals symposium that should be take place in summer 2025.Biosynthesis and Functions of the Nickel-Pincer Nucleotide (NPN) CofactorThe nickel-pincer nucleotide (NPN) cofactor catalyzes the proton-coupled hydride-transfer reactions of selected racemases and epimerases (1-2). This novel organometallic molecule has a square-planar nickel atom that is tri-coordinated by a modified pyridinium mononucleotide, forming C-Ni and two S-Ni bonds (3). Within the active site of enzyme, the nickel is additionally bound by a histidyl residue and in some cases the NPN cofactor is covalently tethered to a lysyl group. Biosynthesis of NPN is a three-step process. LarB uses nicotinic acid adenine dinucleotide (NaAD) as its substrate and catalyzes C5-carboxylation and phosphoanhydride hydrolysis to produce the dicarboxylated pyridine mononucleotide (P2CMN) (4). LarE catalyzes an ATP-dependent sulfur insertion reaction that converts P2CMN into a species with two thiocarboxylic acids (P2TMN) by sacrificial loss of a cysteinyl sulfur atom or by sulfur donation from a [4Fe-5S] cluster (5-6). LarC is a CTP-dependent nickel insertase or cyclometallase that transforms P2TMN into NPN (7-8). Recent developments in understanding the biosynthesis and utilization of the NPN cofactor will be described (9).