Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.99.3 (PRE)
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Two groups of furanocoumarin-inducible cytochrome p450 genes, the CYP6B4 group and the CYP6B17 group, characterized in two closely related tiger swallowtails, Papilio glaucus and Papilio canadensis, are induced to different extents, with generally higher levels of CYP6B transcripts in P. glaucus. To investigate the evolutionary history of these CYP6B genes in the context of their association with furanocoumarin detoxification, we isolated thirteen CYP6B genes from these species. Each of these genes contains an intron at a conserved position (1334 nucleotides from the translation start site), which varies in length due to three insertion/deletions. The proximal 5' end flanking sequence from the transcription initiation site is highly conserved (91-98% nt identity). The sequence 5' to -640 is significantly variable due largely to the presence of three insertion/deletions. The sequence at the 3' end of this region contains a putative xenobiotic response element to xanthotoxin (XRE-xan), important for basal and xanthotoxin-inducible transcription of the P. polyxenes CYP6B1v3 gene, and multiple elements known to regulate vertebrate phase I and II promoters, including an XRE-AhR (Xenobiotic Response Element to Aryl hydrocarbon Receptor), an OCT-1 element (octamer protein binding site), an ARE (Antioxidant Response Element), an EcRE (Ecdysone Response Element), and an imperfect PXR (Pregnane X Receptor) responsive element (PRE). Our analyses of CYP6B genes in these two species indicate that these genes are in an early stage of divergence and that differential exposure of these two species to chemically distinct host plants resulting from geographical isolation has had functional impacts not only on the coding regions of these genes but also on their promoter regions. Thus, changes in p450 regulation as well as catalytic activity may play a role in the evolution of host plant associations in herbivorous insects.
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PMID:CYP6B cytochrome p450 monooxygenases from Papilio canadensis and Papilio glaucus: potential contributions of sequence divergence to host plant associations. 1242 12

The coupling of electron and proton transfer is an important controlling factor in radical proteins, such as photosystem II, ribinucleotide reductase, cytochrome oxidases, and DNA photolyase. This was investigated in model complexes in which a tyrosine or tryptophan residue was oxidized by a laser-flash generated trisbipyridine-Ru(III) moiety in an intramolecular, proton-coupled electron transfer (PCET) reaction. The PCET was found to proceed in a competition between a stepwise reaction, in which electron transfer is followed by deprotonation of the amino acid radical (ETPT), and a concerted reaction, in which both the electron and proton are transferred in a single reaction step (CEP). Moreover, we found that we could analyze the kinetic data for PCET by Marcus' theory for electron transfer. By altering the solution pH, the strength of the Ru(III) oxidant, or the identity of the amino acid, we could induce a switch between the two mechanisms and obtain quantitative data for the parameters that control which one will dominate. The characteristic pH-dependence of the CEP rate (M. Sjodin et al. J. Am. Chem. Soc. 2000, 122, 3932) reflects the pH-dependence of the driving force caused by proton release to the bulk. For the pH-independent ETPT on the other hand, the driving force of the rate-determining ET step is pH-independent and smaller. On the other hand, temperature-dependent data showed that the reorganization energy was higher for CEP, while the pre-exponential factors showed no significant difference between the mechanisms. Thus, the opposing effect of the differences in driving force and reorganization energy determines which of the mechanisms will dominate. Our results show that a concerted mechanism is in general quite likely and provides a low-barrier reaction pathway for weakly exoergonic reactions. In addition, the kinetic isotope effect was much higher for CEP (kH/kD > 10) than for ETPT (kH/kD = 2), consistent with significant changes along the proton reaction coordinate in the rate-determining step of CEP.
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PMID:Switching the redox mechanism: models for proton-coupled electron transfer from tyrosine and tryptophan. 1577 21