Models cytochrome

Table 7. Geometries and inner-sphere reorganisation energies for a number of cytochrome models calculated by the B3LYP method [24]. The haem group was modelled by Fe(porphine) and Met, His, Amt (amino terminal), Cys, Tyr, and Glu were modelled by S(CH3)2, Im, CH3NH2, SCHs", CsHeO", and CH3COO, respectively. All complexes were assumed to be in...

One problem with our system was that the catalyst itself was oxidized fairly easily, so we did not get many catalytic turnovers. Others working on cytochrome models had shown that the catalyst was much more oxidatively stable when the phenyl rings were perfluorinated. Thus we synthesized a perlluorinated version (24) of our previous compound, easily prepared from the porphyrin with four pentafluorophenyl groups by simple reaction with j8-cyclodextrin 6-thiol, which selectively replaced the para fluorines in the phenyl rings. While with the previous catalyst we only achieved three to five turnovers before the catalyst was destroyed, the new fluorinated catalyst performed the same selective hydroxylation of C-6 in the steroid with 187 turnovers. 

Nair PK, Buerk DG, Whalen WJ. Cat carotid body oxygen metabolism and chemoreception described by a two cytochrome model. Am J Physiol 1986 250 H202-H207. 

Figure 3 Two-cytochrome model hypothesizing the oxygen-sensing mechanism in rat carotid body tissue.

Liidemann et al., 1997] Liidemann, S. K., Carugo, O., and Wade, R. C. Substrate access to cytochrome P450cam A comparison of a thermal motion pathway analysis with moleculM dynamics simulation data. J. Mol. Model. 3 (1997) 369-374... 

Metabolism is still a barrier to be overcome. Some QSAR, pharmacophore, protein, and rule-based models are available to predict substrates and inhibitors of a specific cytochrome P450 isoenzyme [47-55]. 

S Modi, MI Paine, MI Sutcliffe, L-Y Lian, WU Pnmi-ose, CR Wolfe, GCK Roberts. A model for human cytochrome P450 2d6 based on homology modeling and NMR studies of substrate binding. Biochemistry 35 4540-4550, 1996. 

Lederer, F., et al. Improvement of the 2.5 A resolution model of cytochrome bsea by redetermining the primary stmcture and using molecular graphics. 

FIGURE 21.20 A model for the mechanism of O9 reduction by cytochrome oxidase. 

FIGURE 21.21 A model for the electron transport pathway in the mitochondrial inner membrane. UQ/UQH9 and cytochrome e are mobile electron carriers and function by transferring electrons between the complexes. The proton transport driven by Complexes I, III, and IV is indicated. 

FIGURE 22.18 Model of the R. viridis reaction center, (a, b) Two views of the ribbon diagram of the reaction center. Mand L subunits appear in purple and blue, respectively. Cytochrome subunit is brown H subunit is green. These proteins provide a scaffold upon which the prosthetic groups of the reaction center are situated for effective photosynthedc electron transfer. Panel (c) shows the spatial relationship between the various prosthetic groups (4 hemes, P870, 2 BChl, 2 BPheo, 2 quinones, and the Fe atom) in the same view as in (b), but with protein chains deleted. 

Figure 11.15 Cation-exchange mia O-LC analysis of a mixture of model proteins (a) the original sample consisting of myoglobin (M), cytochrome C (C) and lysozyme (L) (b) and (c) proteins adsorbed on to and then released from the polyaaylic acid coated fibre with exti ac-tion times of 5 and 240 s, respectively. Reprinted from Journal of Microcolumn Separations, 8, J.-L. Liao et al., Solid phase mia O exti action of biopolymers, exemplified with adsorption of basic proteins onto a fiber coated with polyaaylic acid, pp. 1-4, 1996, with permission from Jolm Wiley Sons, New York.

Catalysis. Cytochrome P-450 model compounds catalyze the epoxidation of alkenes by hypochlorite ions.16 A typical catalyst is OMn(TMP)L+. 

Oae and coworkers oxidized several diaryl, dialkyl and alkyl aryl sulfides to their corresponding sulfoxides using purified cytochrome P-450 obtained from rabbit liver microsomes138. In agreement with expectations, this enzyme did not exhibit much stereospecificity. Some examples including the observed e.e. values are shown by 121-125. A model was proposed to account for the absolute configurations of the sulfoxides produced (126). The sulfur atom is preferentially oxidized from the direction indicated. 

Ekins S, De Groot MJ, Jones JP. Pharmacophore and three-dimensional quantitative structure activity relationship methods for modeling cytochrome P450 active sites. Drug Metab Dispos 2001 29 936-44. 

Korolev D, Balakin KV, Nikolsky Y, Kirillov E, Ivanenkov YA, Savchuk NP, Ivashchenko A A, Nikolskaya T. Modeling of human cytochrome p450-mediated drug metabolism using unsupervised machine learning approach. J Med Chem 2003 46 3631-43. 

Koymans LMH, Vermeulen NPE, Baarslag A, Donne-Op den Kelder GM. A preliminary 3D model for cytochrome P450 2D6 constructed by homology model building. J Comput-Aided Mol Des 1993 7 281-9. 

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