Haem group binding

The difference in properties between the two proteins, whose tertiary structures are very similar (page 67), is due to the superimposed quaternary structure of haemoglobin and the fact that the ease with which any haem group binds O2 is determined by the state of the other three. Starting with deoxyhaemoglobin the first O2 molecule is taken up very slowly, the second and third are taken up more and more readily and the fourth is taken up several hundred times more rapidly than the first hence the sigmoid shape of the curve. 

Figure 2.2 (a) A detailed picture of the haem group and its binding site within myoglobin or... 

Figure 4.2 Hypothetical plasma membrane (PM)-associated structure of FR02. Four histidine residues (white spots) predicted to coordinate two intramembraneous haem groups (white bars) are indicated, as are the tetrapeptide binding sites for FAD and N AD(P)H. The sites of mutations in the FRO gene are indicated (frdl-l,frdl-3) i, inside cell o, outside cell. Reprinted with permission from Nature (Robinson et al., 1999). Copyright (1999) Macmillan Magazines Limited.

Mitochondrial function. NO is able to react with transition metals such as iron, including those contained within haem groups. Even at low NO concentrations there is competition between oxygen and NO for reversible binding to cytochrome c oxidase. If mitochondrial 02 is low respiration slows, which may confer anti-apoptotic benefit to the cell. As NO concentration rises and peroxynitrite is formed, electron transport is irreversibly inhibited, there is increased production of superoxide and other reactive oxygen species and apoptosis occurs. 

Cytochromes are electron-transfer proteins having one or several haem groups. Cytochrome c binds to the protein by one or, more commonly two, thioether bonds involving sulphydryl groups of cysteine residues. The fifth haem iron ligand is always provided by a histidine residue. Cytochrome c has been proved to be a useful model system for studying the relationship between protein structure and thermostability due to the availability of its three-dimensional structure from a wide variety of organisms, both mesophiles and thermophiles. 

The electron transport chain is vital to aerobic organisms. Interference with its action may be life threatening. Thus, cyanide and carbon monoxide bind to haem groups and inhibit the action of the enzyme cytochrome c oxidase, a protein complex that is effectively responsible for the terminal part of the electron transport sequence and the reduction of oxygen to water. 

Thus, for haemoglobin (Hb) the oxygen binding curves are sigmoidal as is shown in the above figure. The fact that n exceeds the unit can be ascribed physically to the fact that attachment of 02 to one haem group increases the binding constant for the next 02, which in turn increases the constant for the next one and so... 

The two polypeptides would also be expected to bind Chi a and pheophytin if this model is correct. The core complex also contains several smaller polypeptides whose functions are obscure. Cyt b-559 is composed of two polypeptides of 9 and 4 kDa, both of which provide histidine residues as ligands for the haem group... 

Cytochrome 6 is a very hydrophobic protein. A model of how it may be folded in the inner mitochondrial membrane may be obtained from its primary structure [204,204a,205] (Fig. 3.9). The haem-binding histidines are positioned pairwise in two segments that traverse the membrane. The haems may therefore be sandwiched between transmembranous helices (cf., cytochrome oxidase haem groups, Section 3.6). This agrees with the perpendicularity between the haem and the membrane planes [206], and with proposed transmembranous electron transfer catalysed by the cytochrome b haems [207,208]. 

The reactive properties of the haem group and Compound I may be affected by the particular protein environment of a specific cytochrome P450. Different P450 isoenzymes show very different substrate specificity, and hydroxylation patterns. These could be the result of orientation or binding effects,188 or the... 

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