The Nickel Pincer Nucleotide (NPN) is a cofactor recently discovered by our group. It harbors a nickel ion coordinated by one carbon and two sulfur atoms, forming a pincer complex well known in organometallic chemistry but previously unseen of in enzymes.
The last step of its biosynthesis is realized by LarC, which insert the nickel ion into the NPN precursor. This reaction, known in organometallic chemistry as a cyclometalation, is characterized by the formation of new metal-carbon and metal-sulfur σ bonds. LarC is therefore the first cyclometallase identified in nature.
The authors found that LarC activity requires Mn2+-dependent CTP hydrolysis and solved the crystal structure of the C-terminal domain of LarC, LarC2, which reveals a hexameric fold and an unprecedented CTP binding pocket.This works
also demonstrates the in vitro synthesis and purification of the NPN cofactor, opening new possibilities for the study of this intriguing cofactor and of NPN-utilizing enzymes.
This study is published in Journal of Biological Chemistry
Reference:Biosynthesis of the nickel-pincer nucleotide cofactor of lactate racemase requires a CTP-dependent cyclometallase. Desguin B, Fellner M, Riant O, Hu J, Hausinger R, Hols P, Soumillion P. J Biol Chem. 2018 Jun 10. pii: jbc.RA118.003741. doi: 10.1074/jbc.RA118.003741.