Iron-molybdenum cofactor, FeMoco structure

Fig. 4. Structure of the iron molybdenum cofactor, FeMoco (after Chan, Kim, and Rees, (4) Bolin et al. (5) and Mayer et al. (7)). The FeMoco is ligated, within the a subunits of the a2j82 tetrameric structure, by residues Hisa442 and Cysa275 (Avl residue numbers).

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... 

Iron molybdenum cofactor, FeMoco was isolated from MoFe protein for the first time in 1977 by Shah and Brill [11]. Since then the cofactor, which naturally attracted much interest as the probable active site of the enzyme, has been thoroughly studied. Although the structure of isolated cofactor remains unknown X-ray studies by Rees et al. have enabled construction of the internal structure of the protein. 

In this section DFT treatments of the iron-molybdenum cofactor and the activation, reduction and protonation of N2 proceeding at this cluster are presented. The earliest of these calculations appeared after publication of the first crystal structures of nitrogenase, and this was well before the discovery of the central atom X. After the discovery of X and its identification as carbon these treatments were, in part, updated. Here we will focus both on the basic theoretical methods to treat the electronic structure of the FeMoco and the reduction of N2 mediated by this cluster. 

Corbett and co-workers compared both the structural and Mo-localized electronic features of the iron-molybdenum co-factor (FeMoco) in isolated MoFe protein and in the ADP AIF4 stabilized complex of the MoFe protein with the Fe protein. The local metal structure of the iron-molybdenum cofactor of nitrogenase in isolated MoFe protein has been determined by XAS. 

The detection of multiple forms of oxidized and semi-reduced FeMoco has important implications with regard to the structure and function of cofactor. Derivation of these species from the iron-molybdenum center in the protein is illustrated in Scheme 1. This behavior is based on the electrochemical and EPR results presented in the previous sections. 

FeMoco can be extracted from the MoFe protein into A(-methylfor-mamide (NMF) solution 32) and has been analyzed extensively using a wide range of spectroscopic techniques both bound to the protein and in solution after extraction from it (33). The extracted FeMoco can be combined with the MoFe protein polypeptides, isolated from strains unable to synthesize the cofactor, to generate active protein. The structure of the FeMoco is now agreed 4, 5, 7) as MoFeTSg homocitrate as in Fig. 4. FeMoco is bound to the a subunit through residues Cys 275, to the terminal tetrahedral iron atom, and His 442 to the molybdenum atom (residue numbers refer to A. vinelandii). A number of other residues in its environment are hydrogen bonded to FeMoco and are essential to its activity (see Section V,E,2). The metal... 

FeMoco, both as a constituent of the FeMo protein and an isolated entity, has been the subject of detailed spectroscopic examination. 57Fe Mossbauer and EPR studies of the cofactor have been interpreted in terms of an S = centre that contains one molybdenum and ca. six irons in a spin-coupled structure. The EPR signal serves as a valuable fingerprint of FeMoco furthermore, release of FeMoco from the FeMo protein produces an EPR spectrum with broader features, but the same profile, thereby indicating that the core of this cluster is little changed by the extraction procedure. Treatment of FeMoco with ca. one equivalent of... 

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