Structures of hemes

Structure of heme. In the hemoglobin molecule, the Fe2+ ion is at the center of an octehedron, surrounded by four nitrogen atoms, a globin molecule, and a water molecule. 

Figure 18.4 Structures of heme/Cu oxidases at different levels of detail, (a) Position of the redox-active cofactors relative to the membrane of CcO (left, only two obligatory subunits are shown) and quinol oxidase (right), (b) Electron transfer paths in mammalian CcO. Note that the imidazoles that ligate six-coordinate heme a and the five-coordinate heme are linked by a single amino acid, which can serve as a wire for electron transfer from ferroheme a to ferriheme as. (c) The O2 reduction site of mammalian CcO the numbering of the residues corresponds to that in the crystal structure of bovine heart CcO. The subscript 3 in heme as and heme 03 signifies the heme that binds O2. The structures were generated using coordinates deposited in the Protein Data Bank, lari [Ostermeier et al., 1997] Ifft [Abramson et al., 2000] (a) and locc [Tsukihara et al., 1996] (b, c).

From the standpoint of the relationship of almost all animal life, the transport of oxygen by heme (also written as haem in some literature) is the basis for respiration. Heme is one of several proteins that contain iron. Others include materials such as myoglobin, ferritin, transferritin, cytochromes, and ferrodoxins. In order to transport the oxygen required, the body of an average adult contains approximately 4 grams of iron. In species such as mollusks, oxygen is transported by proteins that contain copper instead of iron. These are sometimes referred to as the copper blues. The structure of heme is shown in Figure 22.19. 

FIGURE 22.20 The structure of heme. Note that the Fe resides above the plane of the four nitrogen atoms. 

Fig. 3.1 The molecular structure of heme b (also called protoporphyrin IX), the active center of myoglobin, hemoglobin, catalases, and peroxidases, among other heme proteins. 

Tab. 3.1 Main data defining the optimized structure of the FeP(AB) and FeP(lm)(AB) models investigated (AB = CO, NO, 02). Distances are given in A, angles in degrees, and energies in kcal mob1. Porphyrin nitrogens are denoted Np and Nc refers to one of the nitrogen atoms of the axial imidazole. The experimental values correspond to X-ray structures of heme models [18].

Fig. 13. Active site residues in a small-subunit catalase BLC (A) and a large-subunit catalase HPIl (B). The active site residues are labeled, and hydrogen bonds are shown between the serine (113 in BLC and 167 in HPll) and the essential histidine (74 in BLC and 128 in HPll). A single water is shown hydrogen bonded to the histidine. The equivalent water in BLC is located by analogy to the position of the water in HPll. The unusual covalent bond between the N of His392 and the C of Tyr415 in HPll is evident on the proximal side of the heme in B. The flipped orientations of the hemes are evident in a comparison of the two structures, as is the eis-hydroxyspirolactone structure of heme d in B.

Fig. 8. Crystal structure of heme-hemopexin. The crystal structure of the rabbit mesoheme-hemopexin complex (PDB accession number IQHU) (11) showed heme to be bound in a relatively exposed site between the N- and C-domains with one axial His ligand being contributed by the hinge or linking region between the domains and the other by the C-domain. Also noteworthy is the disposition of the heme with its propionate residues pointing inward and neutralized by positive charges in the binding site.

The deoxyheme of the PLL system assumes two states, (a) and (ft) in Scheme 11, and equilibrium is established between diem. The first state (a) is the stable chelate structure, where the heme complex is relatively inactive to oxygen molecules or carbon monoxide, and the helical structure of PLL is partially destroyed. In the second state (ft) chelate formation by the two e-amino side chains of PLL is not perfect, and the heme complex is more active in (ft) than in (a). But the PLL chain is cofled up in an a-helix in (ft). As illustrated in (c), a PLL molecule contains many heme complexes (a) (in our PLL system, [heme]/[residual group of amino acid of PLL] = 1/7.5 and [heme]/[PLL molecule] = 47). When one of the heme complexes combines with molecular oxygen, the chelate structure of heme changes to that of die mixed complex, —NH2—Fe—02, according to Eqs. (12) or (13). The formation of the mixed complex reduces the strain in the PLL chain and the helical structure... 

A major effort on the part of several eminent chemists in the early part of the century led to the elucidation of the structure of heme. The German chemist Hans Fischer successfully synthesized heme in 1929, a feat for which, in 1930,... 

The heme pocket. The helices of hemoglobin (and myoglobin) form a hydrophobic pocket for the heme and provide an environment where the iron atom reversibly binds oxygen. The chemical structure of heme is shown in figure 5.10 and is described in atomic detail in chapters 10 and 14. (Illustration copyright by Irving Geis. Reprinted by permission.)... 

P R E CONTENTS Preface. Stable-Isotope Assisted Protein NMR Spectroscopy in Solution, Brian J. Stockman and John L. Mar-kley. 31P and 1H Two-Dimensional NMR and NOESY-Dis-tance Restrained Molecular Dynamics Methodologies for Defining Sequence-Specific Variations in Duplex Oligonucleotides, David G. Gorenstein, Robert P. Meadows, James T. Metz, Edward Nikonowcz and Carol Beth Post. NMR Study of B- and Z-DNA Hairpins of d[(CG) 3T4(CG)3] in Solution, Sa-toshi Ikuta and Yu-Sen Wang. Molecular Dynamics Simulations of Carbohydrate Molecules, J.W. Brady. Diversity in the Structure of Hemes, Russell Timkovich and Laureano L. Bon-doc. Index. Volume 2,1991, 180 pp. 112.50/E72.50 ISBN 1-55938-396-8... 

Heme degradation Bile pigments exist in both the plant and animal kingdoms, and are formed by breakdown of the cyclic tetrapyrrole structure of heme. In animals this pathway is an excretory system by which the heme from the hemoglobin of aging red blood cells, and other hemoproteins, is removed from the body. In the plant kingdom, however, heme is broken down to form bile pigments... 

Reaction of oxochlorin 54 with methyllithium gave alcohol 62, which was dehydrogenated to the exomethylenechlorin 63 (69LA(725)167). Oxohydro-porphyrins have found multiple interest. A knowledge of the properties of 56 may help to elucidate the structure of heme dy, which most probably is a dioxoisobacteriochlorin and not a chlorin (86JA1352). 

Several lines of evidence are required to completely define the structure of heme groups and their associated ligands (a) optical spectra in the visible region, (b) EPR spectra, (c) the oxidation state of the compound, and (d) proof of the identity of the sixth ligand of the heme iron atom [45], Structural information of other protein elements can be complemented with the use of proteomic tools and X-ray diffraction crystallography. 

Fig. 1. Structure of heme A. This heme is characterized by a hydroxyfarneslyethyl group at position 2 and a formyl group at position 8.

Figure 14 (a) The X-ray structure of heme-bound rabbit hemopexin. (b) shows the /S-propeller structure of individual domains. The figure was created using pdb coordinates Iqhu ... 

Figure 1 The structures of heme (Fe +) and hemin (Fe )- The substituents and pyrrole rings are numbered (A) as most commonly used in biology and (B) according to the lUPAC nomenclature convention.

Figure 2 The structures of heme A, heme C, heme D, and the modified heme found in the CYP4 family of P450 enzymes.

The complex tetrapyrrole ring structure of heme is built up in a stepwise fashion from the very simple precursors sue-cinyl-CoA and glycine (Figure 32-2). The pathway is present in all nucleated cells. From measurements of total bilirubin production, it has been estimated that daily synthesis of heme in humans is 5 to 8mmol/kg body weight. Of this, 70% to 80% occurs in the bone marrow and is used for hemoglobin synthesis. Approximately 15% is synthesized in the liver and is used to produce cytochrome P-450, mitochondrial cytochromes, and other hemoproteins. The pathway is compartmentalized, with some steps occurring in the mitochondrion and others in the cytoplasm. Little is known about the transport of intermediates across the mitochondrial membrane, and no transport defect has yet been reported in the porphyrias. 

---