Cytochrome interactions

No major differences in rate were observed with the ionic form (anion or neutral) of the flavin semiquinone. Comparison of the rates of reduction by a number of flavin analogs suggests that cytochrome interaction occurs through the N(5)-dimethylbenzene region of the isoalloxazine ring. 

There are two main factors that determine the site of metabolism (i) the chemical reactivity and (ii) the preferred orientation of the compound inside the cytochrome cavity. A new technique called MetaSite [32] has been developed in order to consider at the same time, the substrate-cytochrome interaction and the chem-... 

Cytochrome interactions CYP450 inhibitors Norfloxacin > ciprofloxacin > moxifloxacin > levofloxacin = gatifloxacin. 

Chance B. and Nishimura M. (1960), On the mechanism of chlorophyll-cytochrome interaction the temperature insensitivity of light-induced cytochrome oxidation in Chromatium, Proa Natl. Acad. Sci. USA 46, 19-25. 

Fig. 2. Two kinds of photosynthetic bacterial reaction centers based on the nature of binding of the cytochromes to the membrane. P is the primary electron donor T is the intermediate electron acceptor No." refers to Cyt per RC. See text for discussion. Figure adapted from PL Dutton and RC Prince (1978) Reaction center-driven cytochrome interactions in electron and proton translocation and energy coupling. In RK Clayton and WR Sistrom (eds) Photosynthetic Bacteria, p 525. Plenum Press.

Fig. 5. Comparison of kinetics of cytochrome oxidation and reduction in an anaerobic suspension of intact ceils of the photosynthetic bacterium Chromatium at 300,250 and 77 K. Scaies for the absorbance-change and time as well as the calculated rates of cytochrome oxidation and re-reduction are shown. Figure source left panel from Chance and Nishimura (1960) On the mechanism of chiorophyil-cytochrome interaction The temperature insensitivity of tight-induced cytochrome oxidation in Chromatium. Proc Nat Acad Sci, USA. 46 20 and right panei from Chance and DeVault (1964) On the kinetics and quantum efficiency of the chiorophyil-cytochrome reaction. Ber Bunsenges Phys Chem 68 725.

B Chance and M Nishimura (1960) On the mechanism of chiorophyii-cytochrome interaction The temperature insensitivity of tight-induced cytochrome oxidation in Chromatium. Proc Nat Acad Sci, USA. 46 19-24... 

Time-resolved resonance Raman studies of the detailed course of cytochrome interaction with carbon monoxide gives an idea of relaxation and conformational changes in the vicinity of the actual reaction site/ A brief conference report lists rate constants for forward and reverse rate constants for interaction of deoxy-hemerythrin with dioxygen, nitrogen monoxide, hydrazoic acid, formamide, and fluoride/ ... 

The aforementioned model formulation represents the standard case. However, we also wanted to explore the hypothesis that mediators are able to interact with, that is, exchange electrons with, a conductive biofilm matrix. This means that reduced mediators may transfer electrons to the matrix, and likewise, oxidized mediators may accept electrons from the conductive matrix. In this case, dubbed interacting-dual EET, the matrix acts as an extension of the electrode and electron exchange can occur between mediators and the matrix, just as it can between mediators and the electrode surface. Mediators may not have to travel the entire distance between the reducing cell and the oxidizing electrode surface to transfer electrons. We wanted to explore this idea because of the mounting evidence of mediator and cytochrome interactions and the critical role cytochromes play in EAB EET [47-51]. In addition, currently, we have strong experimental evidence that this mechanism is actually involved in electron transfer processes. 

Electron Transport Between Photosystem I and Photosystem II Inhibitors. The interaction between PSI and PSII reaction centers (Fig. 1) depends on the thermodynamically favored transfer of electrons from low redox potential carriers to carriers of higher redox potential. This process serves to communicate reducing equivalents between the two photosystem complexes. Photosynthetic and respiratory membranes of both eukaryotes and prokaryotes contain stmctures that serve to oxidize low potential quinols while reducing high potential metaHoproteins (40). In plant thylakoid membranes, this complex is usually referred to as the cytochrome b /f complex, or plastoquinolplastocyanin oxidoreductase, which oxidizes plastoquinol reduced in PSII and reduces plastocyanin oxidized in PSI (25,41). Some diphenyl ethers, eg, 2,4-dinitrophenyl 2 -iodo-3 -methyl-4 -nitro-6 -isopropylphenyl ether [69311-70-2] (DNP-INT), and the quinone analogues,... 

In addition to halopeiidol, the putative neuroleptics, limcazole (311), lemoxipiide (312), and gevotioline (313) bind to (7-ieceptois as does the dopamine uptake blocker, GBR 12909 (314) and two ligands active at the NMDA receptor, ifenprodil (315) and CNS 1102 (316). NPC 16377, (317) is a selective (7-teceptor ligand. MAO inhibitors and antidepressants also bind to (7-teceptors. Some evidence indicates that (7-teceptors in the brain are in fact a form of cytochrome which may account for the diversity of ligands interacting with (7-sites. 

The L and the M subunits are firmly anchored in the membrane, each by five hydrophobic transmembrane a helices (yellow and red, respectively, in Figure 12.14). The structures of the L and M subunits are quite similar as expected from their sequence similarity they differ only in some of the loop regions. These loops, which connect the membrane-spanning helices, form rather flat hydrophilic regions on either side of the membrane to provide interaction areas with the H subunit (green in Figure 12.14) on the cytoplasmic side and with the cytochrome (blue in Figure 12.14) on the periplasmic side. The H subunit, in addition, has one transmembrane a helix at the car-boxy terminus of its polypeptide chain. The carboxy end of this chain is therefore on the same side of the membrane as the cytochrome. In total, eleven transmembrane a helices attach the L, M, and H subunits to the membrane. 

No region of the cytochrome penetrates the membrane nevertheless, the cytochrome subunit is an integral part of this reaction center complex, held through protein-protein interactions similar to those in soluble globular multisubunit proteins. The protein-protein interactions that bind cytochrome in the reaction center of Rhodopseudomonas viridis are strong enough to survive the purification procedure. However, when the reaction center of Rhodohacter sphaeroides is isolated, the cytochrome is lost, even though the structures of the L, M, and H subunits are very similar in the two species. 

FIGURE l.l Hydrophobic interaction and reversed-phase chromatography (HIC-RPC). Two-dimensional separation of proteins and alkylbenzenes in consecutive HIC and RPC modes. Column 100 X 8 mm i.d. HIC mobile phase, gradient decreasing from 1.7 to 0 mol/liter ammonium sulfate in 0.02 mol/liter phosphate buffer solution (pH 7) in 15 min. RPC mobile phase, 0.02 mol/liter phosphate buffer solution (pH 7) acetonitrile (65 35 vol/vol) flow rate, I ml/min UV detection 254 nm. Peaks (I) cytochrome c, (2) ribonuclease A, (3) conalbumin, (4) lysozyme, (5) soybean trypsin inhibitor, (6) benzene, (7) toluene, (8) ethylbenzene, (9) propylbenzene, (10) butylbenzene, and (II) amylbenzene. [Reprinted from J. M. J. Frechet (1996). Pore-size specific modification as an approach to a separation media for single-column, two-dimensional HPLC, Am. Lab. 28, 18, p. 31. Copyright 1996 by International Scientific Communications, Inc.. Shelton, CT.]... 

Both attractive forces and repulsive forces are included in van der Waals interactions. The attractive forces are due primarily to instantaneous dipole-induced dipole interactions that arise because of fluctuations in the electron charge distributions of adjacent nonbonded atoms. Individual van der Waals interactions are weak ones (with stabilization energies of 4.0 to 1.2 kj/mol), but many such interactions occur in a typical protein, and, by sheer force of numbers, they can represent a significant contribution to the stability of a protein. Peter Privalov and George Makhatadze have shown that, for pancreatic ribonuclease A, hen egg white lysozyme, horse heart cytochrome c, and sperm whale myoglobin, van der Waals interactions between tightly packed groups in the interior of the protein are a major contribution to protein stability. 

Why has nature chosen this rather convoluted path for electrons in Complex 111 First of all. Complex 111 takes up two protons on the matrix side of the inner membrane and releases four protons on the cytoplasmic side for each pair of electrons that passes through the Q cycle. The apparent imbalance of two protons in ior four protons out is offset by proton translocations in Complex rV, the cytochrome oxidase complex. The other significant feature of this mechanism is that it offers a convenient way for a two-electron carrier, UQHg, to interact with the bj and bfj hemes, the Rieske protein Fe-S cluster, and cytochrome C, all of which are one-electron carriers. 

BH3 domain) of the BH3-only proteins binds to other Bcl-2 family members thereby influencing their conformation. This interaction facilitates the release of cytochrome C and other mitochondrial proteins from the intermembrane space of mitochondria. Despite much effort the exact biochemical mechanism which governs this release is not yet fully understood. The release of cytochrome C facilitates the formation of the apoptosome, the second platform for apoptosis initiation besides the DISC. At the apoptosome which is also a multi-protein complex the initiator caspase-9 is activated. At this point the two pathways converge. 

Active caspases 8, 9 and 10 can convert caspase-3, the most abundant effector caspase from its pro-form to its active cleaved form. Cleavage of a number of different substrates by caspase-3 and also by caspase-6 and -7 which are two other executioner caspases besides caspase-3 then results in the typical morphology which is characteristic of apoptosis. Yet, the activation of caspase-3 and also of caspase-9 can be counteracted by IAPs, so called inhibitor of apoptosis proteins. However, concomitantly with cytochrome C also other proteins are released from mitochondria, including Smac/DIABLO. Smac/DIABLO and potentially other factors can interact with IAPs and thereby neutralize their caspase-inhibitory activity. This releases the breaks on the cell death program and allows apoptosis to ensue. 

While it has been known for many years that the N-terminal presequence is sufficient to promote mitochondrial targeting and assembly, the subsequent interaction of the precursor molecule with the outer mitochondrial membrane and the uptake of the protein is still an area of active research. There seems little doubt, however, that there are proteins on the outer mitochondrial membrane which are required for the import process. The function of these proteins is uncertain, but they may act as receptors with the subsequent transfer through the membrane at proteinous pores located at contact sites between the inner and outer membranes. Several proteins have been identified which seem to play an important role as either receptor proteins or part of the import channel (Pfanner et al., 1991). Again, not all proteins seem to depend on this mechanism. Cytochrome c, which is loosely associated with the outer aspect of the inner mitochondrial membrane, can cross... 

Sagir A, Schmitt M, Dilger K, Haussinger D (2003) Inhibition of cytochrome P450 3A relevant drug interactions in gastroenterology. Digestion 68 41 8... 

In be complexes bci complexes of mitochondria and bacteria and b f complexes of chloroplasts), the catalytic domain of the Rieske protein corresponding to the isolated water-soluble fragments that have been crystallized is anchored to the rest of the complex (in particular, cytochrome b) by a long (37 residues in bovine heart bci complex) transmembrane helix acting as a membrane anchor (41, 42). The great length of the transmembrane helix is due to the fact that the helix stretches across the bci complex dimer and that the catalytic domain of the Rieske protein is swapped between the monomers, that is, the transmembrane helix interacts with one monomer and the catalytic domain with the other monomer. The connection between the membrane anchor and the catalytic domain is formed by a 12-residue flexible linker that allows for movement of the catalytic domain during the turnover of the enzyme (Fig. 8a see Section VII). Three different positional states of the catalytic domain of the Rieske protein have been observed in different crystal forms (Fig. 8b) (41, 42) ... 

When the second-site revertants were segregated from the original mutations, the bci complexes carrying a single mutation in the linker region of the Rieske protein had steady-state activities of 70-100% of wild-type levels and cytochrome b reduction rates that were approximately half that of the wild type. In all these mutants, the redox potential of the Rieske cluster was increased by about 70 mV compared to the wild type (51). Since the mutations are in residues that are in the flexible linker, at least 27 A away from the cluster, it is extremely unlikely that any of the mutations would have a direct effect on the redox potential of the cluster that would be observed in the water-soluble fragments. However, the mutations in the flexible linker will affect the mobility of the Rieske protein. Therefore, the effect of the mutations described is due to the interaction between the positional state of the Rieske protein and its electrochemical properties (i.e., the redox potential of the cluster). 

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