Iron center translocation

Fig. 19. The redox-driven translocation of an iron center within a heteroditopic ligand containing a hard compartment [the tris(hydroxamate) donor set, lower level preferred by Fe(III)] and a soft compartment [tris(2, 2 -bipyridine) donor set, upper level chosen by the Fe(II) center). Chemical reduction (with ascorbic acid) and oxidation (with peroxydisulfate) make the iron center translocate from one level to the other...

Figure 2.3 Translocation of an iron center within a two-compartment ligand, driven by the FeIn/Fen redox couple. Fe111 prefers the inner compartment, which provides six oxygen donor atoms and retains a triply negative charge Fe11 chooses the peripheral compartment consisting of three bpy subunits. Consecutive chemical reduction and oxidation makes the metal move back and forth between the two compartments.

Figure 2.6 A square scheme illustrating the pendular motion of an iron center, driven hy the Fe Fe1" redox couple. As judged from voltammetric experiment carried out at varying potential scan rate, the lifetime for both translocation processes is <10 ms.

During the electrochemically switched process, the iron center remains bound to the central phenolate oxygen atom, which acts as a hook. On consecutive oxidation and reduction, the hung metal ion swings from one compartment to the other, following a pendular motion. Probably due to the beneficial assistance of the central phenolate oxygen atom, the translocation... 

Fig. 20. The electrochemically triggered translocation of an iron center within the two-compartment ligand 12, based on the Fe(III)/Fe(II) redox couple. Following consecutive oxidation and reduction processes, the iron center oscillates from the left compartment [Fe(III) state] to the right one [Fe(II) state]. The remaining two coordination sites of the metal center in each oxidation state [both Fe(III) and Fe(II) want to be six-coordinate] are occupied by solvent molecules (S = MeCN)...

In purple photosynthetic bacteria, electrons return to P870+ from the quinones QA and QB via a cyclic pathway. When QB is reduced with two electrons, it picks up protons from the cytosol and diffuses to the cytochrome bct complex. Here it transfers one electron to an iron-sulfur protein and the other to a 6-type cytochrome and releases protons to the extracellular medium. The electron-transfer steps catalyzed by the cytochrome 6c, complex probably include a Q cycle similar to that catalyzed by complex III of the mitochondrial respiratory chain (see fig. 14.11). The c-type cytochrome that is reduced by the iron-sulfur protein in the cytochrome be, complex diffuses to the reaction center, where it either reduces P870+ directly or provides an electron to a bound cytochrome that reacts with P870+. In the Q cycle, four protons probably are pumped out of the cell for every two electrons that return to P870. This proton translocation creates an electrochemical potential gradient across the membrane. Protons move back into the cell through an ATP-synthase, driving the formation of ATP. 

Figure 1 The mitochondrial respiratory chain. Electron transfer (brown arrows) between the three major membrane-bound complexes (I, III, and IV) is mediated by ubiquinone (Q/QH2) and the peripheral protein c)dochrome c (c). Transfer of protons hnked to the redox chemistry is shown by blue arrows red arrows denote proton translocation. NAD+ nicotinamide adenine dinucleotide, FMN flavin mononucleotide, Fe/S iron-sulfur center bH,bi, and c are the heme centers in the cytochrome bc complex (Complex III). Note the bifurcation of the electron transfer path on oxidation of QH2 by the heme bL - Fe/S center. Complex IV is the subject of this review. N and P denote the negatively and positively charged sides of the membrane, respectively...

Microorganisms typically express uptake systems specific for the siderophores that they synthesize as well as siderophores synthesized by other microbes, a strategy that allows them to compete for iron in an environment containing multiple microbial species. The structures of three OM receptors (FecA, FepA, and FhuA) are very similar to one another in that they are all -barrel proteins containing 22 antiparallel /3-strands that form a tube. The N-terminus forms a mobile globular domain that can occupy and occlude the chaimel formed in the center of the tube. When FhuA binds the ferrichrome near the outer surface of the central chaimel, major conformational changes occur both at the outer surface and on the periplasmic face of the receptor. The position of the globular cork domain then shifts to allow the bound siderophore to translocate across the membrane. 

Post-oxidation ferritin species in H-type ferritins (Fe(III)-oxo dimers/trimers) appear to be translocation intermediates trapped in the protein coat by using rapid mixing freeze quenching (milliseconds) and small amounts of iron (average 1.5/ subunit). (Ferroxidation sites in H-type ferritins are in the center of the four-helix bundle of the subunits, based on mutagenesis studies [2]). Under the same conditions, Fe(III) in L ferritins reaches the cavity immediately (polynuclear Fe) (B. H. Huynh and E. C. Theil, unpublished results). Thus, H-type ferritins have rapid oxidation, followed by slow (multi-site ) translocation to the cavity. In contrast, ferroxidation in L-type ferritins is slow, but Fe(IIl) is rapidly (simultaneously ) translocated to the cavity. 

The complex catalyzes electron transfer from reduced UQ to cytochrome c, coupled to the translocation of protons by a mechanism known as the Q cycle [55-57]. This involves the diversion of half of the electrons available from ubiqui-nol oxidation and deprotonation at a site on the outside of the inner mitochondrial membrane (Qo site) to reduce and protonate UQ at a site on the inside of the membrane (Qi site). The pathway for electron transfer across the membrane is provided by the two haem centers (bt and bn) of the mitochondrial gene product cytochrome b. The remainder of the electrons from ubiquinol oxidation pass along the chain to reduce first the Rieske iron sulfur protein (ISP), then cytochrome Cl and then cytochrome c (Fig. 13.1.3). 

Complex IV, or cytochrome c oxidase, was the first of the mitochondrial electron transport complexes to have its molecular stmcture and the internal path of electron transfer revealed by X-ray crystallography. The catalytic core of the complex consists of two subunits. Subunit II contains a binuclear copper center (Cua) that is directly responsible for the oxidation of cytochrome c. From there electrons are passed to haem a and then to the adjacent binuclear center that consists of haem 03 and another copper ion (Cub), which are all held within subunit I (Fig. 13.1.4). Oxygen is bound and reduced between Cub and the iron of haem 03, and access paths for protons from the inside of the membrane and for oxygen from within the membrane have been defined from several crystal stmctures available for bovine and bacterial enzymes. In addition to the protons taken up for the reduction of oxygen, translocation of further protons across the membrane is coupled to electron transfer by a mechanism that is not yet understood (reviewed in Refs. [71, 72]). 

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