Copper oxidase models

COPPER OXIDASE MODELS CATALYTIC ALCOHOL OXIDATION... 

Blue copper electron transfer proteins, 6,712-717 Blue copper oxidases, 6,699 Blue copper proteins, 2, 557 6, 649 Blue electron transfer proteins, 6,649,652 spectroscopy, 6, 651 Blue oxidases copper, 6,654,655 Blueprint process, 6,124 Blue proteins model studies, 6,653 Boleite... 

Mahadevan V, Gebbink RJMK, Stack TDP. 2000. Biomimetic modeling of copper oxidase reactivity. Curr Opin Chem Biol 4 228-234. 

Hammer-Nprskov d-band model, 70, 272-273, 327 Heme-copper oxidase, 610 High Throughput Synthesis of Nanoparticles, 572-574 Hydrogen (underpotential) adsorption, 60-63,254, 471-484, 526 Hydrogen evolution reaction (HER), 31, 79-87... 

Figure 8.3 A model of iron transport across the intestine. Reduction of ferric complexes to the ferrous form is achieved by the action of the brush border ferric reductase. The ferrous form is transported across the brush border membrane by the proton-coupled divalent cation transporter (DCT1) where it enters an unknown compartment in the cytosol. Ferrous iron is then transported across the basolateral membrane by IREG1, where the membrane-bound copper oxidase hephaestin (Hp) promotes release and binding of Fe3+ to circulating apotransferrin. Except for hephaestin the number of transmembrane domains for each protein is not shown in full. Reprinted from McKie et al., 2000. Copyright (2000), with permission from Elsevier Science.

This discussion of copper-containing enzymes has focused on structure and function information for Type I blue copper proteins azurin and plastocyanin, Type III hemocyanin, and Type II superoxide dismutase s structure and mechanism of activity. Information on spectral properties for some metalloproteins and their model compounds has been included in Tables 5.2, 5.3, and 5.7. One model system for Type I copper proteins39 and one for Type II centers40 have been discussed. Many others can be found in the literature. A more complete discussion, including mechanistic detail, about hemocyanin and tyrosinase model systems has been included. Models for the blue copper oxidases laccase and ascorbate oxidases have not been discussed. Students are referred to the references listed in the reference section for discussion of some other model systems. Many more are to be found in literature searches.50... 

Recent work in our laboratories has confirmed the existence of a similar pathway in the oxidation of vindoline in mammals (777). The availability of compounds such as 59 as analytical standards, along with published mass spectral and NMR spectral properties of this compound, served to facilitate identification of metabolites formed in mammalian liver microsome incubations. Two compounds are produced during incubations with mouse liver microsome preparations 17-deacetylvindoline, and the dihydrovindoline ether dimer 59. Both compounds were isolated and completely characterized by spectral comparison to authentic standards. This work emphasizes the prospective value of microbial and enzymatic transformation studies in predicting pathways of metabolism in mammalian systems. This work would also suggest the involvement of cytochrome P-450 enzyme system(s) in the oxidation process. Whether the first steps involve direct introduction of molecular oxygen at position 3 of vindoline or an initial abstraction of electrons, as in Scheme 15, remains unknown. The establishment of a metabolic pathway in mammals, identical to those found in Strep-tomycetes, with copper oxidases and peroxidases again confirms the prospective value of the microbial models of mammalian metabolism concept. 

Electron transfer (continued) intramolecular, from type-1 copper center to trinuclear copper center blue copper oxidases, 40 175-178 iron-sulfur proteins, 47 405, 474-479 kinetic model, flavocytochrome bj, 36 282-283... 

Kopf, M.-A. Karlin, K. D. Models of copper enzymes and heme-copper oxidases, Biomimetic Oxidations Catalyzed by Transition Metal Complexes , Ed. Meunier, B. Imperial College Press London, 2000, pp. 309—362. 

There are numerous reports on the chemical synthesis of models for the active site of galactose oxidase both in the reduced Cu(l) and the oxidized Cu(II) form. We mention only a selection in which EPR is at least used to characterize the complex either on the phenoxy radical or on the copper part, typically in conjunction with X-ray data.48,49 50 A review on structural, spectroscopic and redox aspects of galactose oxidase models is available.51 More important with respect to EPR is the report on the 3-tensor calculation of the thioether substituted tyrosyl radical by ab initio methods but this is borderline to the aspects treated in this review since the copper ion is not involved.52... 

Synthetic models for heme-copper oxidases 04CRV1077. 

Laccases (p-diphenol O2 oxidoreductase EC 1.10.3.2) catalyze the oxidation of p-diphenols with the concurrent reduction of dioxygen to water. However, the actual substrate specificities of laccases are often quite broad and vary with the source of the enzyme [116,117]. Laccases are members of the blue copper oxidase enzyme family. Members of this family have four cupric (Cu +) ions where each of the known magnetic species (type 1, type 2, and type 3) is associated with a single polypeptide chain. In the blue copper oxidases the Cu + domain is highly conserved and, for some time, the crystallographic structure of ascorbate oxidase, another member of this class of enzymes, has provided a good model for the structure of the laccase active site [124,125]. The crystal structure of the Type-2 Cu depleted laccase from Coprinus cinereus at 2.2. A resolution has also been elucidated [126]. 

Although completely adequate models for the metal centers in the blue copper oxidases remain to be developed, substantial progress has been made recently. This comes primarily from insight that has been gained into the in situ structures described above and the resulting sharper focus and more stringent boundary conditions which they impart. 

If both MT-1 and HO-1 mRNA induction by heme-hemopexin involves a copper-redox enzyme in both heme transport (and consequent induction of HO-1 mRNA) and the signaling pathway for MT-1 expression, a plausible working model can be formulated by analogy with aspects of the yeast iron uptake processes and with redox reactions in transport (Figure 5-6). First, the ferric heme-iron bound to hemopexin can act as an electron acceptor, and reduction is proposed to be required for heme release. The ferrous heme and oxygen are substrates for an oxidase, possibly NADH-dependent, in the system for heme transport. Like ferrous iron, ferrous heme is more water soluble than ferric heme and thus more suitable as a transport intermediate between the heme-binding site on hemopexin and the next protein in the overall uptake process. The hemopexin system would also include a copper-redox protein in which the copper electrons would be available to produce Cu(I), either as the copper oxidase or for Cu(I) transport across the plasma membrane to cytosolic copper carrier proteins for incorporation into copper-requiring proteins [145]. The copper requirement for iron transport in yeast is detectable only under low levels of extracellular copper as occur in the serum-free experimental conditions often used. 

As already discussed, the model proposed by Tsukihara et alP depends on the so-scalled H-pathway of proton transfer and on the function of an aspartic acid that is not conserved in the bacterial oxidases. This model also depends crucially on the formyl group and on the hydroxyethyl farnesyl side chain of heme a. Many proton-pumping bacterial oxidases, such as cytochrome boj, from E. coll, have replaced heme a with a protoheme (heme B) that lacks both the formyl and the farnesyl side chain. Therefore, this model is restricted to heme a - containing oxidases, and implies different mechanisms of proton translocation in different members of the heme-copper oxidase superfamily. 

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