Iron-molybdenum nitrogenase

Fig. 15. Structure of the homocitrate component of the nitrogenase iron-molybdenum cofactor.

Lancaster KM, Roemelt M, Ettenhuber P, et al. X-ray emission spectroscopy evidences a central carbon in the nitrogenase iron-molybdenum cofactor. Science. 2011 334 974-7. 

Dean, D.R., Setterquist, R.A., Brigle, K.E., Scott, D.J., Laird, N. F., Newton, W.E., (1990) Evidence that conserved residues Cys-62 and Cys-154 within the Azotobacter vinelandii nitrogenase iron-molybdenum protein a-subuflit are essential for nitrogenase activity but conserved residues His-83 and Cys-88 are not. Mol. Microbiol. 4(9),... 

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). ... 

Biosynthesis of the Nitrogenase Iron-Molybdenum-Cofactor from Azotobacter vinelandii... 

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.

Table 3.4 lists values for A Eq and for some important oxidation and spin states found in bioinorganic molecules. Data are taken from reference 24 and from Table 1 of reference 25 for hemoglobin, myoglobin, and the picket-fence porphyrin model compound, FeTpivPP(l-Melm).25 The myoglobin and hemoglobin model compounds are discussed in Section 4.8.2. Reference 26 provides the Table 3.4 data on iron sulfur clusters found in many bioinorganic species.26 The unusual iron-sulfur and iron-molybdenum-sulfur clusters found in the enzyme nitrogenase are discussed more fully below and in Chapter 6. 

It is recalled that in Chapter 9, Section 2, the electrochemical behaviour of the FeMo cofactor from FeMo-nitrogenase, was reported. It possesses a heteronuclear iron-molybdenum-sulfur (MoFe7S9) cluster, which has similarities with the above discussed iron-sulfur proteins. 

Shah, V.K. and W.J. Brill. Isolation of an iron-molybdenum cofector from nitrogenase. Proc. Natl. Acad. Sci. USA 74,3249-3253 (1977). 

Figure 15. Possible structures for the iron—molybdenum cofactor of nitrogenase.

K), Fe-S cluster assembly (nIfM) and the biosynthesis of the iron molybdenum cofactor, FeMo-co (nifN, B, E, Q, V, H)(5a). It is the last two functions, involving the placement of unusual transition metal sulfide clusters into the nitrogenase proteins, that cause nitrogenase and its components to be appropriately included in this symposium. 

A large number of studies devoted to metal-sulfur centers are motivated by the occurrence of such arrangements at the active site of various metalloenzymes [1-13]. Mononuclear complexes with Mo=0 func-tion(s) and possessing sulfur ligands in their coordination sphere have been extensively investigated since they can be seen as models of the active site of enzymes such as nitrate- and DM SO reductases or sulfite- and xanthine oxidases [1-4]. On the other hand, a large variety of mono-, di-, and polynuclear Mo—S centers have been synthesized in order to produce functional models of the Mo-nitrogenase since the exact nature (mono-, di- or polynuclear) of the metal center, where N2 interacts within the iron-molybdenum cofactor (FeMo—co) of the enzyme is still unknown [4-8]. 

A large part of the research involving metal-sulfur complexes (metal = molybdenum or iron) is aimed at designing functional models of the active site of nitrogenase, the iron-molybdenum cofactor, EeMo—CO [4-8, 12, 13]. Only a very... 

More complex iron-sulfur clusters are also known to exist. These include the iron-molybdenum cofactor of nitrogenase (Thornely and Lowe, 1984) and probably larger clusters in which the only metal is iron (Hagen, 1987). They are characterized by highly anisotropic EPR spectra from S > ground states the nitrogenase cluster, for example is S = j and has EPR features near g = 4 and g = 2. 

Nitrogenase, which catalyzes the reduction of N2 to two molecules of NH3, has a different molybdenum -iron cofactor (FeMo-co). It can be obtained by acid denaturation of the very oxygen-labile iron-molybdenum protein of nitrogenase followed by extraction with d i methyl formamide.655,656 The coenzyme is a complex Fe-S-Mo cluster also containing homocitrate with a composition MoFe7S9-homocitrate (see Fig. 24-3). Nitrogenase and this coenzyme are considered further in Chapter 24. 

One of the enzymes given in Table 23 is nitrogenase, which is responsible for the fixation of dinitrogen to give ammonia. Molybdenum probably serves as the binding site for N2, and is present in the iron-molybdenum cofactor, which is a molybdenum-iron sulfide cluster. Nitrogenase will be considered in Section 63.1.14, which deals with the nitrogen cycle. 

The proteins involved in the reduction of nitrogen to ammonia and other accessible forms contain several such clusters coupled with molybdenum centres. The structure of the central iron-molybdenum cluster at the centre of nitrogenase is shown in Fig. 10-9. Even with the detailed knowledge of this reaction site, the mode of action of nitrogenase is not understood. 

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