Histidine cytochrome

Wang F, Bella J, Parkinson JA, Sadler PJ (2005) Competitive reactions of a ruthenium arene anticancer complex with histidine, cytochrome c and an oligonucleotide. J Biol Inorg Chem 10 147-155... 

Figure C3.2.5. Strongest tunnelling patliways between surface histidines and tire iron atom in cytochrome c. Steps in patliways are denoted by solid lines (covalent bonds), dashed lines (hydrogen bonds), and tlirough-space contacts (dotted lines). Electron transfer distance to His 72 is 5 A shorter tlian in His 66, yet tire two rates are approximately...

Electrons from cytochrome c are transferred to Cu sites and then passed to the heme iron of cytochrome a. Cu is liganded by two cysteines and two histidines (Figure 21.18). The heme of cytochrome a is liganded by imidazole rings of histidine residues (Figure 21.18). The Cu and the Fe of cytochrome a are within 1.5 nm of each other. 

FIGURE 21.18 (a) The Cn site of cytochrome oxidase. Copper ligands inclnde two histidine imidazole groups and two cysteine side chains from the protein, (b) The coordination of histidine imidazole ligands to the iron atom in the heme a center of cytochrome oxidase. 

Cytochromes. A cytochrome is a protein containing a heme with an iron cation bonded to four donor nitrogen atoms in a square planar array. Figure 20-29a shows the structure of cytochrome c, in which a histidine nitrogen atom and a cysteine sulfur atom occupy the fifth and sixth coordination sites of the octahedral iron center. 

An important model system for electron transfer studies is the electron carrier cytochrome c (Cyt c). Its redox center is a heme, coordinated by a histidine and... 

D.R. McMillin, Purdue University In addition to the charge effects discussed by Professor Sykes, I would like to add that structural effects may help determine electron transfer reactions between biological partners. A case in point is the reaction between cytochrome C551 and azurin where, in order to explain the observed kinetics, reactive and unreactive forms of azurin have been proposed to exist in solution (JL). The two forms differ with respect to the state of protonation of histidine-35 and, it is supposed, with respect to conformation as well. In fact, the lH nmr spectra shown in the Figure provide direct evidence that the nickel(II) derivative of azurin does exist in two different conformations, which interconvert slowly on the nmr time-scale, depending on the state of protonation of the His35 residue (.2) As pointed out by Silvestrini et al., such effects could play a role in coordinating the flow of electrons and protons to the terminal acceptor in vivo. 

Peroxidases are heme iron-containing proteins similar in structure to that of cytochromes P450. The major difference is that peroxidases have histidine as the axial ligand instead of cysteine, and there are also other polar amino acids close to the heme iron that help to catalyze the peroxidase function of the enzyme (41). The result is that the peroxidases very rapidly catalyze the reduction of hydroperoxides to alcohols (or water in the case of... 

The distorted octahedral species [10] and [11] are the essential part of the cytochromes acting as redox catalysts. In these, a very specific porphyrin redox potential may have been adjusted by an appropriate choice of the axial ligands exerting a cis effect on the porphyrin system transmitted through the iron atom. In cytochrome c, these axial ligands are the imidazole of a histidine and the thioether function of methionine, as in [10], and in the cytochromes a or b5 they are presumably two imidazoles of histidine, as in [77] (7). 

We may illustrate this approach to the determination of the nuclear factor by the elegant studies performed by Gray and co-workers, who have determined the thermodynamic properties and the rate temperature dependence for the electron transfer between Ru(NH3) covalently bound to the histidine residues of some proteins, and the redox eenter of these proteins [110, 111, 112, 113]. The experimental results obtained for cytochrome c [110] and azurin [111, 112] are very similar. Using the thermodynamic data and the value or the upper limit of Ea reported in these studies, we deduce from Eq. (23) ... 

A variety of physical methods has been used to ascertain whether or not surface ruthenation alters the structure of a protein. UV-vis, CD, EPR, and resonance Raman spectroscopies have demonstrated that myoglobin [14, 18], cytochrome c [5, 16, 19, 21], and azurin [13] are not perturbed structurally by the attachment of a ruthenium complex to a surface histidine. The reduction potential of the metal redox center of a protein and its temperature dependence are indicators of protein structure as well. Cyclic voltammetry [5, 13], differential pulse polarography [14,21], and spectroelectrochemistry [12,14,22] are commonly used for the determination of the ruthenium and protein redox center potentials in modified proteins. 

The axial ligands of yeast cytochrome c. Histidine 21 and Met 85 respectively, not only contribute to the high positive potential of cytochrome c but also control the electronic distribution in cytochrome c in such a way that charge density is concentrated at the reactive heme edge. 

Therefore, we investigated a molecular interaction of cardiolipin with cytochrome c. As shown in Figure 2, cytochrome c consists of 5 helices and inter-helical loops which harbor a heme c prosthehc group by covalent thioether-bonds through cysteine-14 and -17 residues. Ferric ion, centered in the pyrrole ring, is axially liganded by histidine-18 and methionine-80 residue. The lower half of the protein consishng of flexible random coils is a rather soft stmcture and has a space between the heme c plate and P-loops inside the smah basic protein. 

Not all cytochromes from sulfate-reducing bacteria reduce Fe(III) or other metals. D. vulgaris produces a cyt C553, which has a molecular mass of 9 kDa, midpoint redox potential of OmV, and a single heme and the iron atom is coordinated by histidine methionine. It is unclear at this time if the inability of this cyt C553 to reduce metals is due to lack of a bishistidinyl iron coordination or to some other factor, such as steric hinderance owing to orientation of heme in the protein. 

This general approach has, however, serious limitations. The position of the site for attack (and therefore the electron transfer distance involved) is very conjectural. In addition, the vexing possibility, which we have encountered several times, of a dead-end mechanism (Sec. 1.6.4) is always present. One way to circumvent this difficulty, is to bind a metal complex to the protein at a specific site, with a known (usually crystallographic) relationship to the metal site. The strategy then is to create a metastable state, which can only be alleviated by a discernable electron transfer between the labelled and natural site. It is important to establish that the modification does not radically alter the structure of the protein. A favorite technique is to attach (NH3)5Ru to a histidine imidazole near the surface of a protein. Exposure of this modified protein to a deficiency of a powerful reducing agent, will give a eon-current (partial) reduction of the ruthenium(III) and the site metal ion e.g. iron(III) heme in cytochrome c... 

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