Nickel-pincer nucleotide cofactor

Curr Opin Chem Biol. 2018 Dec:47:18-23. doi: 10.1016/j.cbpa.2018.06.019. Epub 2018 Jul 9.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Coenzymes / chemistry
  • Coenzymes / metabolism
  • Lactobacillus plantarum / enzymology
  • Models, Molecular
  • Nickel / chemistry*
  • Nickel / metabolism*
  • Nucleotides / chemistry*
  • Nucleotides / metabolism*
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / metabolism
  • Racemases and Epimerases / chemistry*
  • Racemases and Epimerases / metabolism*


  • Coenzymes
  • Nucleotides
  • Organometallic Compounds
  • Nickel
  • Racemases and Epimerases
  • lactate racemase