Cytochrome model complexes

In 2003, the Di Xia group published an X-ray crystallographic study of substrate and inhibitor molecules at the Qo and Qi site. They intended to compare the structure of the native enzyme (PDB INTM) with the cytochrome bci complex having substrate or inhibitors in the Qo and/or Qi sites. The complex with substrate ubiquinone UQ2 (PDB INTZ) was discussed previously in this section. The complex with the inhibitor antimycin Ai (PDB INTK) will be discussed here. A fourth complex with the ubiquinone-model... 

Figure 7.43 Cytochrome c oxidase model complexes, [(Porphyrin)Fe -OH-Cu"(N4)], as synthesized in reference 149.

The rich spectroscopy and electrochemistry of the heme moiety yields a wealth of opportunities for the denovo heme protein design to evaluate the success of the heme binding site design. Combinations of these spectroscopic and electrochemical methods are elucidating the structure and function of de novo heme proteins and illustrating that they serve as excellent bioinorganic model complexes for simple cytochromes. 

Fig. 17.9 Model of the mechanism of Fe " oxidation by Thioba-cillusferrooxidans. PL-Fe phospholipid bound Fe x enzyme (unidentified) Ru rusticyane, a Cu-containing protein cyt c c-type cytochrome cyt ox cytochrome oxidase complex ATP adenosine 5 -triphosphate (Ghiorse Ehrlich, 1992 with permission).

Nomura H, Athauda SB, Wada H, Maruyama Y, Takahashi K, Inoue H (2006) Identification and reverse genetic analysis of mitochondrial processing peptidase and the core protein of the cytochrome bcl complex of Caenorhabditis elegans, a model parasitic nematode. J Biochem (Tokyo) 139 967-979... 

In the early 1970s it was discovered that P-450 cytochromes are irreversibly inhibited during the metabolism of xenobiotics (1). The formation of a modified heme prosthetic group is associated with enzyme inhibition and subsequent studies have identified these modified complexes as N-alkylated protoporphyrin-IX (2). The chemistry of N-sub-stituted porphyrins was comprehensively reviewed by Lavallee in 1987 (3). Since that time, there have been many significant contributions to this field by several groups. The goal of this chapter is to summarize some of this work as it relates to the mechanism of formation and reactivity of iron N-alkyl porphyrins. Biomimetic model complexes have played an important role in elucidating the chemistry of N-alkyl hemes in much the same way that synthetic iron tetraarylporphyrins have aided... 

The absorption spectra of the model complexes of haem a, made by Lemberg and his collaborators (134), have been taken to indicate that the high-spin Fe(III) haem a complexes have absorption bands at 660 mp while the low-spin Fe(III) haem complexes have bands at 595 mp (135). These data allow an analysis of the spin-states of the cytochromes a. The analysis has been carried out by Williams (135), Vanneste (136), Williams, Lemberg and Cutler (137). 

Molecular Modeling of Inhibitors at Qi and Qo Sites in Cytochrome bci Complex... 

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