Copper proteins active sites

One of the major goals of studying active sites in copper proteins has therefore been to understand the spectroscopic features associated with the active site. This has led to a classification of three general types of copper protein active sites based on their unique spectral features Blue copper, normal copper and coupled binuclear copper. An additional class of copper proteins, the multi-copper oxidases, contains a combination of these three types of copper active sites. A reasonably firm understanding of the optical and EPR spectra of a number of copper proteins has now been achieved1,2K This article presents an overview of these electronic spectral features and their relationship to geometric and electronic structure. 

A series of hemocyanin and tyrosinase active site derivatives (Fig. 23) can be prepared61"66), allowing systematic variation of the binuclear copper active site and chemical perturbation for spectral studies. In the simplest derivative, met-apo, one copper has been removed and the remaining copper oxidized to the spectroscopically accessible Cu(II). Next in complexity is a mixed-valent binuclear copper site. The Cu(II), in this half-met derivative, exhibits open-shell d9 spectroscopic features and the Cu(I), though spectroscopically inaccessible, can still be studied by comparison to the met-apo derivative. Two derivatives have formally binuclear cupric sites met, which is EPR-non-detect-able, and dimer, which exhibits an intense broad EPR signal. Spectroscopic study of these derivatives has led to the present picture of the coupled binuclear copper protein active site shown at the bottom of Fig. 23. 

In addition, work by Solomon s group at Stanford University on copper binding active sites has been particularly significant in terms of establishing the power of variable temperature and field studies. The unique spectral and structural features of the copper-protein active sites and their intermediates have been studied in depth based on a wide range of different spectroscopic techniques. This has provided detailed insights into the nature of these sites that... 

Holland PL, Tolman WB (1999) Three-coordinate Cu(II) complexes structural models of trigonal-planar type 1 copper protein active sites. J Am Chem Soc 121(31) 7270-7271... 

Deeth RJ (2007) Comprehensive molecniar mechanics model for oxidized type I copper proteins active site stmctines, strain energies, and entatic bnlging. Inorg Chem 46 4492... 

Henkel G, Krebs B. Metallothioneins zinc, cadmium, mercury and copper thilates and selenolates mimicking protein active site features - structural aspects and biological implications. Chem Rev 2004 104 801-24. 

Copper is an essential element to most life forms. In humans it is the third most abundant trace element only iron and zinc are present in higher quantity. Utilization of copper usually involves a protein active site which catalyzes a critical oxidation reaction, e.g., cytochrome oxidase, amine oxidases, superoxide dismutase, ferroxidases, dopamine-/ -hydrox-ylase, and tyrosinase. Accordingly, animals exhibit unique homeostatic mechanisms for the absorption, distribution, utilization, and excretion of copper (J). Moreover, at least two potentially lethal inherited diseases of copper metabolism are known Wilson s Disease and Menkes s Kinky Hair Syndrome (I). 

Active Sites, Copper Proteins Oxidases, Copper Proteins with Type 1 Sites, Copper Proteins with Type 2 Sites, Copper Enzymes in Denitrification, Iron-Sulfur Models of Protein Active Sites, Iron-Sulfur Proteins Nickel Enzymes Cofactors and Nickel Models of Protein Active Sites). However, since many metalloenzymes have been found or postulated to incorporate metal-sulfur bonding, it is appropriate that a very short sununary be included here. 

Chalcogenides Solid-state Chemistry Copper Enzymes in Denitrification Copper Hemocyanin/Tyrosinase Models Copper Proteins Oxidases Copper Proteins with Dinuclear Active Sites Copper Proteins with Type 1 Sites Copper Proteins with Type 2 Sites Iron Sulfitf Models of Protein Active Sites Iron-Snlfiir Proteins Nickel Enzymes Cofactors Nickel Models of Protein Active Sites Polynuclear Organometallic Cluster Complexes. 

Table 1. Biologically Important Proteins with Copper Ion Active Sites...

There has been further model work aimed at elucidating the role of copper in copper-proteins. Gagn et al. have reported the preparation of a family of five-co-ordinate adducts of Cu and, while not suggesting these as models for any particular enzyme system, they point out that their existence means that consideration of copper(i) active site structures must include the possibility of five-co-ordination. Spectroscopic studies of blue copper models have included work with compounds containing copper(ii)—sulphur bonds and/or pseudotetrahedrally co-ordinated copper(ii) e.g. refs. 207—212). It appears that the metal sites in cobalt(ii) sub-... 

Solomon El, Penfield KW, Wilcox DE (1983) Active Sites in Copper Proteins. An Electric Structure Overview. 53 1-56... 

The enzymes are protein molecules having globular structure, as a rule. The molecular masses of the different enzymes have values between ten thousands and hundred thousands. The enzyme s active site, which, as a rule, consists of a nonproteinic organic compound containing metal ions of variable valency (iron, copper, molybdenum, etc.) is linked to the protein globule by covalent or hydrogen bonds. The catalytic action of the enzymes is due to electron transfer from these ions to the substrate. The protein part of the enzyme secures a suitable disposition of the substrate relative to the active site and is responsible for the high selectivity of catalytic action. 

In the blue, Type I copper proteins plastocyanin and azurin, the active-site structure comprises the trigonal array [CuN2S] of two histidine ligands and one cysteine ligand about the copper,... 

Theoretical calculations have been carried out on a number of zinc-containing enzymatic systems. For example, calculations on the mechanism of the Cu/Zn enzyme show the importance of the full protein environment to get an accurate description of the copper redox process, i.e., including the electronic effects of the zinc ion.989 Transition structures at the active site of carbonic anhydrase have been the subject of ab initio calculations, in particular [ZnOHC02]+, [ZnHC03H20]+, and [Zn(NH3)3HC03]+.990... 

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