[FeFe]‐Hydrogenase Cofactor Assembly

摘要: This article highlights recent advances in our understanding of the biosynthetic pathway for active site H-cluster assembly [FeFe]-hydrogenases. The is composed a [4Fe–4S] cubane bridged via one cysteine thiolate to 2Fe subcluster; subcluster further coordinated by carbon monoxide, cyanide, and bridging dithiolate ligands. Biosynthesis occurs through stepwise modification simple Fe–S cluster precursors; these chemical modifications are carried out three gene products denoted HydE, HydF, HydG. Maturation [FeFe]-hydrogenase requires presence preformed cluster, indicating that HydG directed toward biosynthesis subcluster. HydE both radical S-adenosylmethionine (SAM) enzymes utilize CX3CX2C motif bind site-differentiated [4Fe–4S]2+/+ clusters promote reductive cleavage SAM into methionine 5′-deoxyadenosyl responsible hydrogen atom abstraction from substrate. In an extraordinary biochemical reaction, uses this chemistry catalyze degradation tyrosine p-cresol glycine-like intermediate; accessory, C-terminal then degrades latter intermediate cyanide monoxide. presumed be ligand unknown HydF contains N-terminal GTPase domain Fe–S-cluster-binding binds [2Fe–2S] clusters; evidence suggests former modified form precursor on HydF. role GTP hydrolysis maturation remains largely unexplained; however, it may related gating protein–protein interactions between reactions catalyzed can thought as specific events designed fine-tune reactivity; not only do transformations themselves have direct links important early Earth, but with their canonical likely very ancient. modern diversity observed superfamily explained evolutionarily recruitment distinct protein domains impart substrate activation capabilities. Recruitment discussed context made nitrogenase system where intriguing parallels [FeFe]-hydA FeMo-cofactor clearly exist. Keywords: hydrogenase; H-cluster; radical SAM; S-adenosylmethionine; GTPase; cluster assembly; cluster