Iron protein effect

Low DW, Hill MG. Backbone-engineered high-potential iron proteins effects of active-site hydrogen bonding on reduction potential. J. Am Chem. Soc. 2000 122 11039-11040. 

The destructive effect of dioxygen on the iron and molybdenum-iron proteins is thought to result from the oxidation of the clusters, and the formation of superoxide and peroxide which oxidize the proteins irreversibly. In view of this, it is remarkable that aerobic and facultative organisms can fix dinitrogen. The cyanobacteria evolve dioxygen photosynthetically and simultaneously fix dinitrogen 1447... 

Iron is stored in intestinal mucosal cells as ferritin (an iron/protein complex) until needed by the body. Iron deficiency results from acute or chronic blood loss, from insufficient intake during periods of accelerated growth in children, or in heavily menstruating or pregnant women. Therefore it essentially results from a negative iron balance due to depletion of iron stores and inadequate intake, culminating in hypochromic microcytic anemia. Supplementation with ferrous sulfate is required to correct the deficiency. Gastrointestinal disturbances caused by local irritation are the most common adverse effects caused by iron supplements. 

Adrenal and testis non-heme iron proteins equally exhibit extrinsic multiple Cotton effects with three distinct maxima. The peaks of adrenodoxin appaer at 530 mp, 480 mp, and 360 mp and the troughs at 580 mp and 400 mp (Fig. 4). The peaks of testis protein appear at 530 mp, 475 mp, and 355 mp and the troughs at 580 mp and 390 mp. The characteristics of the principal effects in the above two proteins and spinach ferredoxin are summarized in Table 6. 

These results consistently indicate that the three non-heme iron proteins exhibit multiple Cotton effects. Their ORD also shows these effects. Further, it is seen that the optical activity of the three proteins is very similar, differing only by minor shifts in wavelength and intensity of the individual components. This striking similarity leads us to believe that the stereospecific configuration of the iron chromophore is essentially identical in these proteins. However, the behavior of these proteins differs... 

The diversity in oxidation-reduction potentials (Table 9) can not be accounted for as iron environmental differences among these non-heme iron proteins, since the fundamental structures of iron coordination must be identical (Section III-A and B). Therefore, it is of interest that the secondary environmental effect causes such a great variety in oxidation-reduction potentials. 

Lipid hydroperoxides are fairly stable molecules under physiological conditions, but their decomposition is catalysed by transition metals and metal complexes (O Brien, 1969). Both iron(II) and iron(III) are effective catalysts for hydroperoxide degradation, but the former is more so (Halliwell and Gutteridge, 1984). These include complexes of iron salts with low molecular weight chelates, non-haem iron proteins, free haem, haemoglobin, myoglobin. 

Vanadium nitrogenase is produced by certain bacteria grown in molybdenum-deficient environments. It is effective in the reduction of N2 and other nitrogenase substrates, although with less activity than the Mo—Nase. The enzyme resembles the Mo analogue (see Sections 17-E-10 and 18-C-13) in the construction and structure of the prosthetic groups, as well as in its functions.101 It consists of a FeV protein, FeVco, and an iron protein (a 4Fe—4S ferredoxin). 

B. Redesign of Nonheme Iron Proteins. In heme protein redesign described above, the heme prosthetic group largely dictates the active site structure. Redesign focuses mainly on the proximal and distal sides of the heme, causing minimal effects on the overall protein scaffolds. This is not necessarily the case for nonheme metalloproteins in which metal sites are not as dominant and small changes may have more dramatic effects on the protein folds and stability. 

In particular we refer to high-potential iron proteins (HP) and to cubane-like model complexes, which are the only examples of JT effect in biomolecules containing metal clusters we have found in literature " ... 

For the process in vivo flavodoxin is the external electron donor. For isolated nitrogenase, dithionite 8204 is traditionally used as electron donor. If dithionite is the external donor, the oxidized iron protein with 2MgADP (after the electron is transferred) then dissociates from the MoFe protein. This dissociation, which initially seemed necessary for enzyme function, is, however, apparently a result of the salt effect of dithionite, the concentration of which for effective electron transfer must be sufficiently large. 

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