Heme units

Each heme unit in myoglobin and hemoglobin contains one ion bound to four nitrogen donor atoms in a square planar arrangement. This leaves the metal with two axial coordination sites to bind other ligands. One of these sites is bound to a histidine side chain that holds the heme in the pocket of the protein. The other axial position is where reversible binding of molecular oxygen takes place. 

The binding and release of oxygen by hemoglobin can be represented as a ligand-exchange equilibrium at the sixth coordination site on the Fe ion. Each of the four polypeptide chains of hemoglobin contains one heme unit, so... 

The studies of Hasinoff [53] on the recombination rate of carbon monoxide and the heme units after photodissociation of carboxy ferrous microperioxidase come close to satisfying the requirements for observing the effects of anisotropic reactivity and rotational diffusion on the rate of a translational diffusion-limited reaction. In Chap. 2, Sect. 5.6, the details of this study were briefly mentioned. Hasinoff found that the rate of recombination was substantially diffusion-limited in all three aqueous solvents used at 260 K, but at higher temperatures, the rate of reaction of the encounter pair, feact, was a significant factor in determining the overall rate of recombination (see Fig. 9). The observed rate coefficient of recombination, feobs, was separated into the rate coefficient of diffusive formation of encounter pairs, feD, and the rate coefficient of reaction of encounter pairs, fcact, with the Collins and Kimball expression, eqn. (26)... 

Hill [263]. All of these could reasonably explain the measured reduction of the encounter pair formation rate coefficient. Being based on a more rigorous foundation, the Schmitz and Schurr model is to be preferred. From this analysis, Hasinoff [53] suggests that the heme unit in microperoxidase has a reactive site which subtends a semi-angle of 31° at the heme centre. 

It would be interesting to study the effect of changing the size of peptides associated with the heme unit, but only in the plane of the heme unit. The rotational relaxation time would be markedly affected but not the anisotropic reactivity of the heme unit. 

Fig. (4). The Emerging Structure of Hemozoin. (A) Spectroscopically based model of hemozoin as a linear coordination polymer of heme units linked by a propionate linkage. (B) Hydrogen-bonded model of hemozoin from X-ray powder diffraction data showing two strands of heme units hydrogen bonded via the other propionic acid groups. (C) Current X-ray model of hemozoin revealing a hydrogen-bonded network of heme dimers linked by reciprocating axial propionate linkages.

A qualitative structural model has been proposed by these authors. Before the photolysis, the 6-coordinated Fe2+ ion is located in the plane of the porphyrin ring of the heme unit. Rupture of the coordination bond... 

Cytochrome c Oxidase. This is a ubiquitous enzyme that catalyzes the terminal step in the four-electron reduction of 02 to 2H20. It contains both heme iron and copper and there are two kinds of copper sites, CuA and CuB, in each of which there is an association of copper with heme iron. The CuB site seems to have one copper atom linked to a heme unit, but details are still obscure.37 From modeling studies and EXAFS data, opinion presently favors some sort of Fe—X—Cu bridge... 

All the remaining questions focus on comparisons of CCP, MMB, and CAT. The first question addressed is Can the differences in the active site of CCP, MMB, and CAT account for the differences in their observed electromagnetic properties MMB and CCP (55, 56) have been found to have the same heme unit, a ferric protoporphyrin-IX with a water and an imidazole as axial ligands. CAT has a single... 

Energies of the lowest lying sextet, quartet and doublet states were calculated for each of the heme units studied. The geometries of the complexes were taken from crystal structures and simplified to unsubstituted porphyrins. The orientations of the porphyrin macrocycles were such that the pyrrole nitrogens were on the x- and y-axes. The choice of the lowest energy configurations for each state was as follows ... 

The ability of the method to predict the patterns of spin state behavior in these model complexes lends credence to the use made of it in the second part of these studies, to further characterize the heme units in the resting state of four heme proteins. 

These studies of the active sites of four heme proteins appear to allow a consistent explanation of their observed electromagnetic properties and confirm the central role of the heme unit itself in determining these properties. 

Vedani 1985, Damewood 1990, Ferguson 1991 Heme (ferryl heme unit with valproic acid)... 

Hemoglobin consists of four polypeptide chains (two a subunits and two 3 subunits), each of which carries a heme unit. Hemoglobin has more nonpolar amino acids than myoglobin. When each subunit is folded, some of these remain on the surface. The van der Waals attraction between these hydrophobic groups is what stabilizes the quaternary structure of the four subunits. 

Figure 4 Physical characterization of hemozoin. (a) The axial propionate linkages between heme units in FIZ are seen by FT-IR fingerprints of C = 0 and C-O stretching at 1664 and 1211 cm , respectively, (b) Characteristic 2 1 peaks are seen at T-. 21° and 24° 28 for (i) native and (ii) synthetic FIZ. Absent from these aggregates is the 23° 28 peak observed in the diffraction pattern of (iii) substrate hemin chloride, (c) Electron micrograph of FIZ in P. falciparum infected RBC where (i) is the host RBC, (ii) is the parasite, and (iii) is the DV. Image reproduced with kind permission of Springer Science and Business Media (23). (d) SEM image of uniform BFI crystals.

Slater A, Swiggard W, Orton B, Hitter W, Goldberg D, Cerami A, Henderson G. An iron-carboxylate bond links the heme units of malaria pigment. Proc. Natl. Acad. Sci. U.S.A. 1991 88 325-329. Noland G, Briones N, Sullivan D Jr. The shape and size of hemozoin crystals distinguishes diverse Plasmodium species. Mol. Biochem. Parasitol. 2003 130 91-99. 

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