title: Emerging paradigms for complex iron-sulfur cofactor assembly and insertion.
abstract: [FeFe]-hydrogenses and molybdenum (Mo)-nitrogenase are evolutionarily unrelated enzymes with unique complex iron-sulfur cofactors at their active sites. The H cluster of [FeFe]-hydrogenases and the FeMo cofactor of Mo-nitrogenase require specific maturation machinery for their proper synthesis and insertion into the structural enzymes. Recent insights reveal striking similarities in the biosynthetic pathways of these complex cofactors. For both systems, simple iron-sulfur cluster precursors are modified on assembly scaffolds by the activity of radical S-adenosylmethionine (SAM) enzymes.   Radical SAM enzymes are responsible for the synthesis and insertion of the unique nonprotein ligands presumed to be key structural determinants for their respective catalytic activities. Maturation culminates in the transfer of the intact cluster assemblies to a cofactor-less structural protein recipient. Required roles for nucleotide binding and hydrolysis have been implicated in both systems, but the specific role for these requirements remain unclear. In this review, we highlight the progress on [FeFe]-hydrogenase H cluster and nitrogenase FeMo-cofactor assembly in the context of these emerging paradigms.
authors.affiliation: Department of Chemistry and Biochemistry and the Astrobiology Biogeocatalysis Research Center, Montana State University, Bozeman, Montana 59717, USA. john.peters@chemistry.montana.edu
authors.forename: John W
authors.initials: JW
authors.lastname: Peters
authors.forename: Joan B
authors.initials: JB
authors.lastname: Broderick
mesh_terms: D001419:Bacteria / Q000201:enzymology / Q000378:metabolism*; D001934:Branchial Region / Q000201:enzymology / Q000378:metabolism; D003067:Coenzymes / Q000737:chemistry / Q000378:metabolism*; D006864:Hydrogenase / Q000737:chemistry / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000378:metabolism*; D008983:Molybdoferredoxin / Q000737:chemistry / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D013455:Sulfur / Q000378:metabolism*
chemical_list: D003067:Coenzymes; D007506:Iron-Sulfur Proteins; D008983:Molybdoferredoxin; D013455:Sulfur; D012436:S-Adenosylmethionine; D007501:Iron; C118830:iron hydrogenase; D006864:Hydrogenase