Nitrogenase: A Nucleotide-Dependent Molecular Switch

NifH: Structural and Mechanistic Similarities with Proteins Involved in Diverse Biological Processes

“…Two helices, each from one subunit, pointing with their N-termini towards the [4Fe-4S] cluster and forming a helix-cluster-helix angle of 105°, is a remarkable feature of CompA [54] . Such similar architecture has also been noted in NifH, revealing a helix-cluster-helix angle of 150° [ 55] . Further, as observed in the NifH complex with MoFe protein in the , the CompA also probably opens to an angle of 180° upon ATP binding.…”

Catalysis-dependent selenium incorporation and migration in the nitrogenase active site iron-molybdenum cofactor

“…The reduction of substrates by nitrogenase entails multiple cycles of association and dissociation between two component proteins for sequential transfer of electrons ( Burgess and Lowe, 1996 ; Howard and Rees, 2006 ; Hoffman et al, 2014 ; Hageman and Burris, 1978 ). In the transient complex, electrons are transferred from the [4Fe:4S]-cluster of the homodimeric Fe-protein to the MoFe-protein in a reaction requiring adenosine triphosphate (ATP) hydrolysis ( Burgess and Lowe, 1996 ; Howard and Rees, 1994 ). The MoFe-protein, an (αβ) 2 tetramer, contains two types of unique metal centers per catalytic αβ-unit: the P-cluster [8Fe:7S] and the FeMo-cofactor [7Fe:9S:C:Mo]- R -homocitrate ( Kim and Rees, 1992 ; Einsle et al, 2002 ; Spatzal et al, 2011 ).…”

Conformational variability in structures of the nitrogenase iron proteins from Azotobacter vinelandii and Clostridium pasteurianum

“…The two-component nitrogenase system consists of the iron protein (Fe-protein) and molybdenumiron protein (MoFe-protein) working in concert to effect nitrogen reduction (for recent reviews, see Howard & Rees, 1994, 1996Peters et al, 1995;Burgess & Lowe, 1996;Muchmore et al, 1996;Seefeldt & Dean, 1997). Under conditions of molybdenum depletion, alternative nitrogenase systems containing either vanadium or iron that are homologous to the molybdenum-containing`c onventional'' nitrogenase system may be induced (reviewed by Eady, 1996).…”

“…The complex structure indicates that while relatively minor changes occur in the MoFe-protein structure relative to the uncomplexed protein, large-scale conformational changes are evident in Fe-protein, both within and between the subunits. The role of ATP hydrolysis in this process is not well understood, but there is suggestive evidence that ATP hydrolysis is coupled to a series of conformational changes, especially in the Fe-protein, that function as a molecular clock to properly sequence different events in the reaction (Howard & Rees, 1994).…”

“…Given this diversity in biochemical and sequence properties, crystallographic analyses of both Av2 and Cp2 should permit an assessment of the range of structural variability present in the Feprotein family. A clear mechanistic picture of nitrogenase, including Fe-protein, will provide clues to the complex coupling of nucleotide hydrolysis and electron transfer, and will have implications for signal transduction in multiprotein assemblies (Georgiadis et al, 1992;Thorneley, 1992;Howard, 1993;Howard & Rees, 1994). Fe-protein displays structural similarity to other nucleotide-binding proteins, including signal transduction molecules such as G-proteins and ras, and energy transduction systems such as myosin.…”