Reductase model

Recent attention has turned to novel, porphyrin-related macrocycles such as the porphy-cenes82-85 and the nitrite reductase model iron complexes of porphinone, porphindione, and iso-bacteriochlorin.86... 

The idea of common ancestry of the different ribonucleotide reductases is difficult to test at present because protein sequencing studies have not yet begun. Exchangeability of subunits, possible among the calf thymus and mouse enzymes , has not much been tried. We have seen small but significant stimulation of enzyme activity when the separated, inactive subunits U1 of algal (Scenedesmus) ribonucleotide reductase and B 2 of E. coli were recombined, but not in the reverse combination (B1 -t- U2) . The many individual differences in enzyme structure like Mg or Ca " requirement for subunit interaction, variations in the radical environment as expressed in slightly different ESR spectra (Fig. 3), or details of allosteric effector pattern, do not in principle contradict our reductase model but will in reality severely limit its experimental verification. 

Liu, Y, C. DeSilva, and M.D. Ryan (1997). Electrochemistry of nitrite reductase model compounds. 6. Voltammetric and spectroelectrochemical studies of iron(II) nitrosyl complexes with porphyrins, hydroporphyrins and porphinones. Inorg. Chim. Acta 258, 247-255. 

Fig. 2. Structure of mercuric reductase (modeled after the crystal structure of ScHiERiNG et al. 1991). is indicated bound to four cysteine sulfurs (see text). NADPH and FAD are perpendicular to the plane of the page. Amino (N) and carboxyl (C) termini of the amino acid backbone are indicated, as is the dithiol (5-5, although probably reduced cysteines in vivo) near the amino terminus. The central dot represents the twofold rotational axis...

Product formation kinetics in mammalian cells has been studied extensively for hybridomas. Most monoclonal antibodies are produced at an enhanced rate during the Gq phase of the cell cycle (8—10). A model for antibody production based on this cell cycle dependence and traditional Monod kinetics for cell growth has been proposed (11). However, it is not clear if this cell cycle dependence carries over to recombinant CHO cells. In fact it has been reported that dihydrofolate reductase, the gene for which is co-amplified with the gene for the recombinant protein in CHO cells, synthesis is associated with the S phase of the cell cycle (12). Hence it is possible that the product formation kinetics in recombinant CHO cells is different from that of hybridomas. 

HMG CoA-Reductase HMG-CoA-Reductase Inhibitors Homologous Desensitization Homologous Proteins Homologous Recombination Homology Modeling Hormonal Contraceptives Hormone Replacement Therapy (HRT)... 

Sjbberg B-M (1997) Ribonucleotide Reductases - A Group of Enzymes with Different Metallosites and a Similar Reaction Mechanism. 88 139-174 Slebodnick C, Hamstra BJ, Pecoraro VL (1997) Modeling the Biological Chemistry of Vanadium Structural and Reactivity Studies Elucidating Biological Function. 89 51-108 Smit HHA, see Thiel RC (1993) 81 1-40... 

Dvornik, D. (1987). Animal models of diabetic complications and their relation to aldose reductase inhibition. In Aldose Reductase Inhibition (ed. D. Porte) pp. 153-219. McGraw-Hill, New York. 

The general influence of covalency can be qualitatively explained in a very basic MO scheme. For example, we may consider the p-oxo Fe(III) dimers that are encountered in inorganic complexes and nonheme iron proteins, such as ribonucleotide reductase. In spite of a half-filled crystal-field model), the ferric high-spin ions show quadrupole splittings as large as 2.45 mm s < 0, 5 = 0.53 mm s 4.2-77 K) [61, 62]. This is explained... 

Figure 1.4 Left panel Space filing model of the structure of bacterial dihydrofolate reductase with methotrexate bound to the active site. Right panel Close-up view of the active site, illustrating the structural complementarity between the ligand (methotrexate) and the binding pocket. See color insert. Source Courtesy of Nesya Nevins.

---