Cytochrome evolution

In this picture of cytochrome evolution, point mutations occur at random along the DNA which codes for the amino acid sequence, and the protein produced from this mutated DNA is tested in the organism for its ability to operate as a functioning cytochrome. If the molecule is impaired, then the mutation is deleterious, and if the molecule is ineffective, the mutation is lethal. We never see these lethal mutations in the sequence record because the unfortunate carriers of them are weeded out. Residues such as histidine-18 and methionine-80 are absolutely essential. 

Dickerson, R. E., 1980. Cytochrome rand die evolution of energy metabolism. Scientific American 242(3) 137—153. 

In contrast to common usage, the distinction between photosynthetic and respiratory Rieske proteins does not seem to make sense. The mitochondrial Rieske protein is closely related to that of photosynthetic purple bacteria, which represent the endosymbiotic ancestors of mitochondria (for a review, see also (99)). Moreover, during its evolution Rieske s protein appears to have existed prior to photosynthesis (100, 101), and the photosynthetic chain was probably built around a preexisting cytochrome be complex (99). The evolution of Rieske proteins from photosynthetic electron transport chains is therefore intricately intertwined with that of respiration, and a discussion of the photosynthetic representatives necessarily has to include excursions into nonphotosynthetic systems. 

Lewis, D.F.V. (1996). Cytochromes P450—Contains a very useful chapter on the evolution of forms of cytochrome P450. 

THE ROLE OF CYTOCHROMES P450 IN BIOSYNTHESIS AND EVOLUTION OF GLUCOSINOLATES... 

Duffy JE, Hay ME (2001) The ecology and evolution of marine consumer-prey interactions. In Bertness MD, Gaines SD, Hay ME (eds) Marine community ecology. Sinauer, Sunderland, pp 131-158 Duisken M, Sandner F, Blomeke B, Hollender J (2005) Metabolism of 1,8-cineole by human cytochrome P450 enzymes identification of a new hydroxylated metabolite. Biochim Biophys Acta 1722 304-311... 

In the above-mentioned examples, the prediction of CYP-mediated compound interactions is a starting point in any metabolic pathway prediction or enzyme inactivation. This chapter presents an evolution of a standard method [1], widely used in pharmaceutical research in the early-ADMET (absorption, distribution, metabolism, excretion and toxicity) field, which provides information on the biotransformations produced by CYP-mediated substrate interactions. The methodology can be applied automatically to all the cytochromes whose 3 D structure can be modeled or is known, including plants as well as phase II enzymes. It can be used by chemists to detect molecular positions that should be protected to avoid metabolic degradation, or to check the suitability of a new scaffold or prodrug. The fully automated procedure is also a valuable new tool in early-ADMET where metabolite- or mechanism based inhibition (MBI) must be evaluated as early as possible. 

Ghersi-Egea JF, Minn A, Daval JL, Jayyosi Z, Arnould V, et al. 1989. NADPH cytochrome P-450(c) reductase biochemical characterization in rat brain and cultured neurons and evolution of activity during development. Neurochem Res 14 883-887. 

Rozman D, Stromstedt M, Waterman MR. 1996. The three human cytochrome P450 lanosterol 14 alpha-demethylase (CYP51) genes reside on chromosomes 3, 7, and 13 structure of the two retrotransposed pseudogenes, association with a line-1 element, and evolution of the human CYP51 family. Arch Biochem Biophys 333 466-474. 

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