Diiron sites

Protein Source Diiron site function Diiron-binding sequence motif Diiron(III) solvent bridge... 

Figure 10.3. The Hr subunit and its diiron site. Dioxygen binds reversibly to the iron labeled Fe2 (Stenkamp 1994). Reprinted with permission from Xiong et al. (2000), copyright 2000 American Chemical Society.

Proteins with dinuclear iron centres comprise some well studied representatives like ribonucleotide reductase (RNR), purple acid phosphatase (PAP), methane monooxygenase hydroxylase (MMOH), ruberythrin and hemerythrin. The latter is an oxygen carrier in some sea worms it has been first characterized within this group and has thus laid the foundation to this class of iron coordination motif. Ruberythrin is found in anaerobic sulfate-reducing bacteria. Its name implies that, in addition to a hemerythrin-related diiron site another iron is coordinated in a mononuclear fashion relating to rubredoxin which is an iron-... 

The thermodynamic stability of the binuclear site has been demonstrated by the spontaneous assembly of [Fe20(02CR)2L2] (13) from ferric salts in the presence of water, an alkyl carboxylate salt, and a tridentate nitrogen donor ligand L that can cap an octahedral face on iron (8). Suitable ligands include tris(pyrazolyl)borates and 1,4,7-triazacyclononanes. Structure (13) is in essence a portion of the basic ferric acetate structure. The complexes are excellent physical and structural models of the diiron sites and model some aspects of reactivity including redox activity and interconversion of the oxo and hydroxo bridge. 

Hemeiythrin (Hr) was the first of this group to be characterized in detail and is thus considered the prototype. (As will be seen later, however, this notion is incorrect, as Hr turns out to be distinct from the other members of this class.) The structures of deoxyhemeiythrin and oxyhemerythrin (Figure 6) show a novel (p-hydroxo or oxo)bis(p-carboxylato)diiron site with five terminal His ligands [27], The binding of 02 at the vacant sixth terminal site of deoxyHr involves the transfer of two electrons from the diiron(II) center and the hydron of the hydroxo... 

The oxidative mechanism of RNR R2 differs from that of MMOH in requiring an additional electron, since Tyrl22 provides only a single electron. This electron is needed to convert P to X. It has been shown that external reductants such as excess Fe(II) or ascorbate can provide this electron in in vitro reconstitution reactions [87,97], Since the diiron site is buried 10 A below the protein surface, a long-range electron transfer pathway is required to deliver this extra electron to the diiron center. Such a pathway involving a number of amino acid residues has been proposed from examining the crystal structure of R2 [98],... 

A similarity in the visible spectra of some /i-oxo-di-/i-acetato Mn(III) dinuclear complexes to the spectrum of Mn catalase has been noted (168-174). Reaction of hydrotris(l-pyrazolyl)borate, [HB(pz)3], or 1,4,7-triazacyclononane (TACN) with Mn(0Ac)3 2H20 results in the formation of the dinuclear complexes [Mn2in0(0Ac)2(HB(pz)3)2] (168) and [Mn/1 0(0Ac)2(TACN)2]2+ (169). Selected structural parameters are given in Table VII. The dimanganese cores of the complexes are essentially identical to those of some /i-oxo-di-/i-carboxylato diiron(III) complexes (177,178), which have been shown to be excellent structural models of the diiron site in methemerythrin (Fig. 8) (179). 

The theoretical treatments of the MMO meehanism are based on high level quantum mechanical methods that form models of the diiron site in which the ligand geometry is built from X-ray erystallographie studies and other biophysieal techniques. The caleulations of Siegbahn and eoworkers based on density functional theory that were described briefly above led to... 

Hendrich, M. P., Fox, B. G., Andersson, K. K., Debrunner, P. G., and Lipscomb, J. D., 1992, Ligation of the diiron site of the hydroxylase component of methane monooxygenase. An electron nuclear double resonance study, J. Biol. Chem. 267 261n269. 

FIGURE 5. Three-dimensional structure of the radical-diiron site in protein R2.The iron centre, the RTF, andTyrl22 in met R2 (A). The hydrophobic pocket close to Tyrl22 (B). For clarity, some iron ligands have been omitted from B. 

The mouse R2 radical is considerably less stable than the E. coli R2 radical (Nyholm et al., 1993). Strikingly, the iron ions are not very tightly bound to the mouse protein, and purified mouse R2 is obtained with only 0.1 Fe/R2 and has to be reconstituted before use (Mann et al., 1991). This is probably an effect of the more open structure of the iron-radical site as seen from the crystal structure (Kauppi et al., 1996). Possibly, the relatively high midpoint potential of ca. lOOmV for the mouse diiron site also affects the radical stability. 

Bollinger, J. M., Krehs, C., Vicol, A., Chen, S. X., Ley, B. A., Edmondson, D. E., and Huynh, B. H., 1998, Engineering the diiron site of Escherichia coli ribonucleotide reductase protein R2 to accumulate an intermediate similar to H-peroxo, the putative peroxodiiron(III) complex from the methane monooxygenase catalytic cycle. J. Am. Chem. Soc. 120 1094nl095. 

Davydov, A., Schmidt, P. P., and Gr%oslund, A., 1996a, Reversible red-ox reactions of die diiron site in the mouse ribonucleotide reductase R2 protein. Biochem. Biophys. Res. Comimm. 219 213n218. 

Mixed valent containing a diiron site where the oxidation states of the irons are not the same... 

Metalloenzymes with diiron sites where the metal ions are bridged by carboxylates (i.e. glutamate, aspartate) have emerged as an important class of enzyme see Iron Proteins with Dinuclear Active Sites)Several members of this... 

Mossbauer parameters have been instrumental in characterizing diiron sites in model systems. The electronic environment can be assessed by the Mossbaner parameters. At 4 K, the isomer shift 8 for iron(II) centers typically falls between 1.06 and 1.35 mm s, whereas the qnadrupole splitting AEq varies from 1.95 to 3.28mms. The isomer shift for diferric species is characteristically small compared to that for diferrons centers. Typical valnes fall between 0.40... 

The class of proteins referred to in the title includes only those containing nonheme, non-sulfur diiron sites. Several reviews of various members of this class of proteins are available,although none are simultaneously comprehensive and completely up-to-date. This state of affairs signals neither neglect nor lack of interest, but rather the rapid expansion and development of knowledge in this area. Though stiU dwarfed by the numbers of heme or iron sulfur proteins, the list of... 

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