Heme groups

We assume in the following that the ligand is bound in a binding pocket of depth 6 —a = 7 A involving a potential barrier AU = 25 kcal/mol, similar to that of streptavidin (Chilcotti et al., 1995). We also assume that the diffusion coefficient of the ligand is similar to the diffusion coefficient of the heme group in myoglobin (Z) = 1 A /ns) as determined from Mofibauer spectra (Nadler and Schulten, 1984). 

Gofactors. Frequendy proteins exist in their native state in association with other nonprotein molecules or cofactors, which are cmcial to their function. These may be simple metal ions, such as Fe " in hemerythrin or Ca " in calmodulin a heme group, as for the globins nucleotides, as for dehydrogenases, etc. 

The most conspicuous use of iron in biological systems is in our blood, where the erythrocytes are filled with the oxygen-binding protein hemoglobin. The red color of blood is due to the iron atom bound to the heme group in hemoglobin. Similar heme-bound iron atoms are present in a number of proteins involved in electron-transfer reactions, notably cytochromes. A chemically more sophisticated use of iron is found in an enzyme, ribo nucleotide reductase, that catalyzes the conversion of ribonucleotides to deoxyribonucleotides, an important step in the synthesis of the building blocks of DNA. 

Figure 3.10 Schematic diagram of the glohin domain. The eight a helices are labeled A-H. A-D are red, E and F green, and G and H blue. The heme group is shown in white. (Adapted from orlginais provided by A. Lesk.)...

To answer the first question, Lesk and Chothia examined in detail residues at structurally equivalent positions that are involved in helix-heme contacts and in packing the a helices against each other. After comparing the nine globin structures then known, the 59 positions they found that fulfilled these criteria were divided into 31 positions buried in the interior of the protein and 28 in contact with the heme group. These positions are the principal determinants of both the function and the three-dimensional structure of the globin family. 

Figure 12.14 The three-dimensional structure of a photosynthetic reaction center of a purple bacterium was the first high-resolution structure to be obtained from a membrane-bound protein. The molecule contains four subunits L, M, H, and a cytochrome. Subunits L and M bind the photosynthetic pigments, and the cytochrome binds four heme groups. The L (yellow) and the M (red) subunits each have five transmembrane a helices A-E. The H subunit (green) has one such transmembrane helix, AH, and the cytochrome (blue) has none. Approximate membrane boundaries are shown. The photosynthetic pigments and the heme groups appear in black. (Adapted from L. Stryer, Biochemistry, 3rd ed. New York ...

FIGURE 15.26 Oxygen and carbon monoxide binding to the heme group of myoglobin. 

A model for the allosteric behavior of hemoglobin is based on recent observations that oxygen is accessible only to the heme groups of the a-chains when hemoglobin is in the T conformational state. Perutz has pointed out that the heme environment of /3-chains in the T state is virtually inaccessible because of steric hindrance by amino acid residues in the E helix. This hindrance dis-... 

This equation states that the ratio of oxygenated, heme groups (F) to 02-free heme (1 F) is equal to the nth power of the PO2 divided by the apparent dissociation constant, K. 

Cytochromes were first named and classified on the basis of their absorption spectra (Figure 21.9), which depend upon the structure and environment of their heme groups. The b cytochromes contain iron—protoporphyrin IX (Figure 21.10), the same heme found in hemoglobin and myoglobin. The c cytochromes contain heme c, derived from iron-protoporphyrin IX by the covalent attachment of cysteine residues from the associated protein. UQ-cyt c... 

NO-sensitive GC represents the most important effector enzyme for the signalling molecule NO, which is synthesised by NO synthases in a Ca2+-dependent manner. NO-sensitive GC contains a prosthetic heme group, acting as the acceptor site for NO. Formation of the NO-heme complex leads to a conformational change, resulting in an increase of up to 200-fold in catalytic activity of the enzyme [1]. The organic nitrates (see below) commonly used in the therapy of coronary heart disease exert their effects via the stimulation of this enzyme. 

Besides NO, other sGC-activating substances have been reported Carbon monoxide (CO) is known to bind to heme groups with high affinity but has been shown to activate the enzyme only marginally (three- to fivefold). The compound YC-1 ([3-(5 -hydroxymethyl-2 -fury 1)-1-benzyl indazole]) is a prototype of a new class of so-called NO-sensitisers. YC-1 causes a tenfold activation of NO-sensitive GC. Pharmacologically more interesting, YC-1 increases GC s sensitivity towards NO and CO suggesting potential beneficial effects of... 

Molecular oxygen is transported throughout the body by attaching to the iron(ll) atom in the heme group of hemoglobin. The iron(ll) atom lies at the center of a square planar complex formed by nitrogen atoms. When the O, molecule attaches to the iron, the plane of the heme group becomes distorted. 

Figure 7. Mechanism of the proton-translocating ubiquinol cytochrome c reductase (complex III) Q cycle. There is a potential difference of up to 150 mV across the hydrophobic core of this complex (potential barrier represented by the vertical broken line). Cytochromes hour and b N are heme groups on the same peptide subunits of complex III which can transfer electrons across the hydrophobic core. The movement of two electrons provides the driving force to transfer two protons from the matrix to the cytosol. Diffusion of UQ and UQHj, which are uncharged, in the hydrophobic core, and lipid bilayer of the inner membrane is not influenced by the membrane potential (see Nicholls and Ferguson, 1992).

Fig. 8. (a) Structure of the full-length Rieske protein from bovine heart mitochondrial bci complex. The catalytic domain is connected to the transmembrane helix by a flexible linker, (b) Superposition of the three positional states of the catalytic domain of the Rieske protein observed in different crystal forms. The ci state is shown in white, the intermediate state in gray, and the b state in black. Cytochrome b consists of eight transmembrane helices and contains two heme centers, heme and Sh-Cytochrome c i has a water-soluble catalytic domain containing heme c i and is anchored by a C-terminal transmembrane helix. The heme groups are shown as wireframes, the iron atoms as well as the Rieske cluster in the three states as space-filling representations. 

Catalase is a hemoprotein containing four heme groups. In addition to possessing peroxidase activity, it is able to use one molecule of H2O2 as a substrate electron donor and another molecule of H2O2 as an oxidant or electron acceptor. 

Imately 65 X 55 X 50 It Is composed of four polypeptide chains each resembling quite closely the myoglobin chain The three dimensional structure of the subunits Is held together by weak noncovalent bonds The polar amino acid side chains are In contact with the solvent, and the nonpolar residues are located In the Interior of the molecule or In regions which form the contacts between chains The heme group Is located In a pocket In each chain residues In contact with heme are Invariable ( e are the same In different mammalian hemoglobins) and the bonds between heme and chain are hydrophobic Interactions Contacts between like chains (a-a are... 

T gure l, Tyx)-dimensioml presentation of the o-chain of human hemoglobin. 9, residues in contact th the heme group residues that participate in the ctrpi contact , residues that participate in the ai pt contact (3). 

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