NIFS

NifS is a PLP-dependent cysteine desulfurase enzyme found in nitrogen-fixing bacteria and archaea. It plays a central role in the biosynthesis of iron-sulfur (Fe-S) clusters that are essential for nitrogenase activity and for many other Fe-S proteins. NifS typically functions together with NifU, a scaffold protein that receives sulfur from NifS and transfers it to target apoproteins.

The enzymatic reaction catalyzed by NifS involves removal of sulfur from l-cysteine to form alanine and a persulfide intermediate on a catalytic cysteine within NifS. The sulfur is then transferred to NifU, from which it is incorporated into Fe-S clusters that mature apo-nitrogenase components (such as the MoFe protein and Fe protein) as well as other Fe-S enzymes. The process requires the pyridoxal phosphate (PLP) cofactor bound in the active site.

Genetically, nifS genes are often located in nif operons alongside nifU and other nitrogen fixation genes, reflecting their coordinated role in assembling nitrogenase Fe-S clusters under diazotrophic conditions. Biochemically, NifS and NifU form a functional relay for sulfur during Fe-S cluster maturation.

Structure and evolutionally related systems: NifS is generally considered a dimeric PLP-dependent enzyme. Its bacterial counterparts are related to other cysteine desulfurases such as IscS and SufS, and homologous enzymes exist in eukaryotes, where the mitochondrial NFS1 protein participates in a broader Fe-S assembly machinery with ISCU. NifS is therefore part of a conserved family that links cysteine desulfurase activity to Fe-S cluster biogenesis.