Heme iron structures activation

Brown CA, Pavlosky MA et al (1995) Spectroscopic and theoretical description of the electronic structure of S = 3/2 iron-nitrosyl complexes and their relation to O2 activation by non-heme iron enzyme active sites. J Am Chem Soc 117 715-732... 

P450 2C9 crystal structure information also served in docking and molecule dynamics operations to simulate the simultaneous binding of a heteroactivator and a substrate [ 17]. N SAID substrates were thereby positioned nearer to the heme than the heteroactivator. For the latter, limited conformational freedom was discovered because of the reduced active-site volume. The presence of an activator shortened the substrate-heme iron distances leading to an increase in the number of catalytic... 

Cytochrome c can easily be extracted from tissue particles by dilute salt solutions. It was isolated by Keilin and Hartree in 1930 and shown to contain a porphyrin ring structure. In 1933 Zeilen and Reuter established that cytochrome c was a heme (iron-porphyrin) protein. Slightly different forms of cytochrome a were distinguished in yeast and bacteria by Keilin in 1934 and the different properties of cytochrome a and a3 by Tamiya et al. in 1937. The identity of cytochrome 03, the enzyme which activates oxygen with Warburg s atmungsferment, was proposed by Keilin in 1939. Cytochrome a/a3 was renamed cytochrome oxidase by Malcolm Dixon (1939). The oxidation route then offered was ... 

The coordination sphere around the ferrous iron center is almost octahedral with the heteroscorpionate clamp causing a deviation of 4-6° from the ideal 90° angle. A comparison with very high-resolution protein structures such as IPNS or CAS clearly shows a good correspondence of structure 4b in distances and angles with the active sites of the non-heme iron enz5unes (Table I). 

Perhaps the most fundamental fimctional property of a heme prosthetic group at the active site of a heme protein is the relative stability of the reduced and oxidized states of the heme iron. A number of structural characteristics of the heme binding environment provided by the apo-protein have been identified as contributing to the regulation of this equilibrium and have been reviewed elsewhere 82-84). Although a comprehensive discussion of these factors is not possible in the space available here, they can be summarized briefly. The two most significant influences of the reduction potential of the heme iron appear to be the dielectric constant of the heme environment 81, 83) and the chemical... 

The enzymes of this type that have been characterized contain some type of redox-active cofactor, such as a flavin (3), or a metal ion (heme iron, non-heme iron, or copper), or both (4-6). Our understanding of the mechanism of these enzymes is most advanced in the case of the heme-containing enzyme cytochrome P450. But in spite of the availability of a crystal structure of an enzyme-substrate complex (7) and extensive information about related reactions of low molecular weight synthetic analogues of cytochrome P450 (8), a detailed picture of the molecular events that are referred to as "dioxygen activation" continues to elude us. 

Active Site Structure of Rubredoxin There are several non-heme iron-sulphur proteins that are involved in electron transfer. They contain distinct iron-sulphur clusters composed of iron atoms, sulphydryl groups from cysteine residues and inorganic or labile sulphur atoms or sulphide ions. The labile sulphur is readily removed by washing with acid. The cysteine moieties are incorporated within the protein chain and are thus not labile. The simplest type of cluster is bacteria rubredoxin, (Cys-S)4 Fe (often abbreviated FelSO where S stands for inorganic sulphur), and contains only non labile sulphur. It is a bacterial protein of uncertain function with a molecular weight of 6000. The single iron atom is at the centre of a tetrahedron of four cysteine ligands (Fig.). 

The AAHs are functionally and structurally similar, which is reflected in a high sequence similarity (Fig. 1). Phylogenetic and functional analyses place a protozoan PAH close to the ancestor sequence of the AAHs, thus aiding to define the evolutionary history of this enzyme family (10). While bacterial PAH is monomeric, the mammalian AAHs are tetrameric enzymes that consist of three domains an N-terminal regulatory ACT domain, a central catalytic domain that includes a non-heme iron at the active... 

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