Multicopper oxidases, functions

Zheng W, Li QE, Su L, Yan YM, Zhang J, Mao LQ. 2006. Direct electrochemistry of multicopper oxidases at carhon nanotubes noncovalently functionalized with cellulose derivatives. Electroanalysis 18 587-594. 

The goal of our research on the multicopper oxidases has been to determine the spectral features of the type 3 (and type 2) centers, to use these spectral features to define geometric and electronic structural differences relative to hemocyanin and tyrosinase, and to understand how these structural differences contribute to their variation in biological function. The hemocyanins and tyrosinases reversibly bind and activate dioxygen whereas the multicopper oxidases catalyze its four-electron reduction to water. 

Brouwers, G.J., et al., Bacteria Mn2+ oxidation multicopper oxidases An overview of mechanisms and functions, Geomicrobiol. J., 17, 1, 2000b. 

The constrained nature of the copper center in BCB domains reduces its reorganization energy, which is considered an important feature for their function in long-range electron transfer processes. They are capable of tunneling electrons, usually over 10- to 12-A distances, intramolecu-larly within the same protein (in the case of multicopper oxidases and nitrite reductases) or intermolecularly between a donor and an acceptor protein (in the case of cupredoxins) in a thermodynamically favorable environment. 

In the yeast Sa. cerevisiae the functional homologue of ceruloplasmin is Fet3. It is a multicopper oxidase that displays ferroxidase activity similar... 

The high-affinity pathway involves oxidation of Fe to Fe by the ferroxidase FET3 and subsequent transport of Fe " " across the plasma membrane by the permease FTRl. FET3p is a member of the family of multicopper oxidases, which include ascorbate oxidase, laccase, and ceruloplasmin (see Chapter 14), and does not become functional until it is loaded with copper intracellularly through the activities of the copper chaperone ATX Ip and the copper transporter CCC2p. It appears that Fe " " produced by FET3 is transferred directly to FTRl, and does not equilibrate with the bulk phase, as is illustrated in Fig. 7.13. This is almost certainly achieved by the classic metabolite-channeling mechanism, a common feature of multifunctional enzymes. 

Intramolecular ET between distinct copper centers is part of the catalytic cycles of many copper-containing redox enzymes, such as the multicopper oxidases, ascorbate oxidase, and ceruloplasmin, as well as the copper-containing nitrite reductases. Examination of internal LRET in these proteins is of considerable interest as it may also provide insights into the evolution of selected ET pathways in particular, whether and how the enzymes have evolved in order to optimize catalytic functions. With the increase in the number of known high-resolution 3D structures of transition metal containing redox enzymes, studies of structure-reactivity relationships have become feasible and indeed many have been carried out during the last two decades. 

FET3 gene product of S. cerevisiae is a multicopper oxidase and plays a key role in iron metabolism of this eukaryote has underpinned the function of ceruloplasmin in vertebrate iron transport. By virtue of its ferroxidase activity, ceruloplasmin converts Fe(II) into Fe(III), which binds to the iron-binding protein transferrin. Ceruloplasmin is critical for iron egress from some cell types. The transport system responsible for iron release into plasma has not been identified. ... 

Nakamura et al. 191) have carried out a fairly comprehensive study of ascorbate oxidase from cucumber Cucumis sativus) peel. The Cu + was shown to undergo cychc reduction and oxidation and the pH-activity curve was demonstrated to be bell-shaped with a broad maximum between pH 5.5 and 7. The velocity of the reaction depended on both ascorbate and O 2 concentrations with ifm02 lmM and = mM at 25 °C. Azide was found to inhibit uncompetitively and Ki = 0.2 mM. Ascorbate oxidase appears to be substantially similar in its structure-function relationships to all the other known multicopper oxidases. 

Multiple coppers in a laccase can slice up the lignin net... A. Levasseur et al. Exploring laccase-like multicopper oxidase genes from the ascomycete Trichoderma reesei A functional, phylogenetic and evolutionary study. 2010. BMCBiocfeem. 11, p. 32. DOI 10.1186/ 1471-2091-11-32. 

Kataoka K, Komori H, Ueki Y, Konno Y, Kamitaka Y, Kurose S, Tsujimura S, Higuchi Y, Kano K, Seo D, Sakurai T. Stmcture and function of the engineered multicopper oxidase CueO from Escherichia coir, deletion of the methionine-rich heUcal region covering the substrate-binding site. J Mol Biol 2007 373 141-152. 

Sakurai T, Kataoka K. Structure and function of type I copper in multicopper oxidases. Cell Mol Life Sci 2007 64 2642-2656. 

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