Nitrogenase cofactor, FeMoco

As well as donating electrons to the MoFe protein, the Fe protein has at least two and possibly three other functions (see Section IV,C) It is involved in the biosynthesis of the iron molybdenum cofactor, FeMoco it is required for insertion of the FeMoco into the MoFe protein polypeptides and it has been implicated in the regulation of the biosynthesis of the alternative nitrogenases. 

Fig. 1. Schematic illustration of the enzyme nitrogenase being composed of the molybdenum-iron (MoFe) protein, an oc2p2 tetramer with two unique iron-sulfur clusters (P-cluster) and two iron-molybdenum cofactors (FeMoco), and the iron protein with one [4Fe-4S]-cluster and two ATP binding sites.

Nitrogenases from various nitrogen fixing organisms seem to contain the same Fe/Mo/S structural unit that occurs as an extractable cofactor (FeMoco) (2). Extracts of the Fe-Mo component protein from inactive mutant strains of different microorganisms that do not contain the Fe/Mo/S center are activated upon addition of the FeMoco. 

In the related V clusters a similar core structure is seen but with shorter Fe4S3 bond distances. The ten atom Fe4( 43-S)3( 4-S)3 core is contained in the FeMoco structure, Figure 3, with the same bond connectivity and similar spatial arrangement and, as such, probably provides the best starting point for development of higher nuclearity clusters related to the nitrogenase cofactors. 

The conversion of dinitrogen to ammonia is one of the important processes of chemistry. Whereas the technical ammonia synthesis requires high temperature and pressure (1), this reaction proceeds at room temperature and ambient pressure in nature, mediated by the enzyme nitrogenase (2). There is evidence that N2 is bound and reduced at the iron-molybdenum cofactor (FeMoco), a unique Fe/Mo/S cluster present in the MoFe protein of nitrogenase. Although detailed structural information on nitrogenase has been available for some time (3), the mechanism of N2 reduction by this enzyme is still unclear at the molecular level. Nevertheless, it is possible to bind and reduce dinitrogen at simple mono- and binuclear transition-metal systems which allow to obtain mechanistic information on elemental steps involved... 

Nitrogen Fixation in Nature The nitrogenase enzyme is a two-component protein that consists of an electron-transfer Fe protein and a catalytic protein [85]. Three different nitrogenase enzymes are known, which differ primarily in the nature of the putative active site within the catalytic protein. The most common form is the MoFe protein, in which the active site for nitrogen reduction, the so-called FeMo cofactor (FeMoco), is composed of seven irons, one molybdenum, and nine sulfides... 

Enzymes containing molybdenum are of two types (1) Nitrogenases, which are required for converting atmospheric nitrogen to nitrogen compounds (NH3, for example) nitrogenases contain a characteristic polymetal atom cluster species called the iron-molybdenum cofactor, FeMoco (Section 17-E-10). (2) The other Mo enzymes, all of which have some variant of a characteristic molybdenum cofactor, Moco. 

Fig. 2. The fe -weighted EXAFS data associated with the iron K-edge of the iron-molybdenum cofactor (FeMoco) extracted from the FeMo-protein of the nitrogenase of Klebsiella pneumoniae, and its Fourier transform (19). 

S-adenosylmethionine (SAM or AdoMet) superfamily, aconitase, and others), enzymes that contain Fe-S heteroatomic clusters (nitrogenase iron-molybdenum cofactor (FeMoco), carbon monoxide dehydrogenase (CODH), and acetyl CoA synthase (ACS)), and enzymes that contain unique ligation sets around specialized iron centers ([NiFe] and [FeFe] hydrogenases) (Figure 1). ... 

The enzyme system responsible for N2 reduction, called the nitrogenase complex, consists of two separate proteins. As outlined in Figure 20.4, one protein-called component I, nitrogenase, or molybdenumiron protein-catalyzes the reduction of N2, and the other-called component II, nitrogenase reductase, or iron protein-transfers electrons from ferredoxin or flavodoxin to component I. Both component I and component II contain Fe4S4 iron-sulfur clusters, and component I also contains molybdenum, in the form of a tightly bound iron-molybdenum cofactor (FeMoCo). 

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