Enzymes Cytochromes

Despite considerable efforts very few membrane proteins have yielded crystals that diffract x-rays to high resolution. In fact, only about a dozen such proteins are currently known, among which are porins (which are outer membrane proteins from bacteria), the enzymes cytochrome c oxidase and prostaglandin synthase, and the light-harvesting complexes and photosynthetic reaction centers involved in photosynthesis. In contrast, many other membrane proteins have yielded small crystals that diffract poorly, or not at all, using conventional x-ray sources. However, using the most advanced synchrotron sources (see Chapter 18) it is now possible to determine x-ray structures from protein crystals as small as 20 pm wide which will permit more membrane protein structures to be elucidated. 

The link with the final electron acceptor, O2, is the enzyme cytochrome c oxidase which spans the inner membrane of the mitochondrion. It consists of cytochromes a and a3 along with two, or possibly three, Cu atoms. The details of its action are not fully established but the overall reaction catalysed by the enzyme is ... 

Blomberg MRA, Siegbahn PEM. 2006. Quantum chemistry applied to the mechanisms of transition metal containing enzymes—Cytochrome c oxidase, a particularly challenging case. J Comput Chem 27 1373. 

The mechanism of hydrogen sulfide toxicity is in part similar to that of cyanide. Like cyanide, hydrogen sulfide can inhibit the enzyme cytochrome oxidase resulting in tissue hypoxia. Specific health effects are discussed in greater detail below. 

Enzymes Cytochrome cdi Nitrate and Cytochrome c Peroxidase Vilmos Fulop, Nicholas J. Watmough, and Stuart J. Ferguson... 

Fig. 21.4 Three-dimensional structure of the enzyme cytochrome P450 oxidoreductase. The cofactors FAD and FMN are depicted in light blue. Loop regions are represented by cylindrical rods (yellow) a-helices and /(-sheets (in white) are represented by ribbons and arrows, respectively. Resonance assignments for the residues located in the key loops regions [30] highlighted in purple and red were obtained with a 3D SEA-HNCA-TROSY experiment.

Description of the model. Benzene and its metabolites (phenol, catechol, and hydroquinone) were assumed to compete for the same reaction site on the enzyme cytochrome P-450 2E1. In addition, phenol can undergo both oxidation and conjugation, although the enzymes for each of these reactions are localized in different compartments of the liver, and competition between them is thereby regulated. 

Once formed, the MV+ radical acts as a reducing agent and chemically reduces the redox centre of a biological molecule (illustrated here with the example of the electro-inactive enzyme, cytochrome-c), as follows ... 

Constitutive e3q>ression and localization of the major drug metabolizing enzyme, cytochrome P4502D in human brain. Brain Res Mol Brain Res 103 49-61. 

---