Oxygenation copper enzymes

Oxygen activation is a central theme in biochemistry and is performed by a wide range of different iron and copper enzymes. In addition to our studies of the dinuclear non-heme iron enzymes MMO and RNR, we also studied oxygen activation in the mononuclear non-heme iron enzyme isopenicillin N synthase (IPNS). This enzyme uses O2 to transform its substrate ACV to the penicillin precursor isopenicillin N [53], a key step in the synthesis of the important P-lactam antibiotics penicillins and cephalosporins [54, 55],... 

Copper enzymes are involved in reactions with a large number of other, mostly inorganic substrates. In addition to its role in oxygen and superoxide activation described above, copper is also involved in enzymes that activate methane, nitrite and nitrous oxide. The structure of particulate methane mono-oxygenase from the methanotrophic bacteria Methylococcus capsulatus has been determined at a resolution of 2.8 A. It is a trimer with an a3P33 polypeptide arrangement. Two metal centres, modelled as mononuclear and dinuclear copper, are located in the soluble part of each P-subunit, which resembles CcOx subunit II. A third metal centre, occupied by Zn in the crystal, is located within the membrane. 

Laccase was discovered in 1883 by Yoshida (4), who found that the latex of the Chinese or Japanese lacquer tree rapidly hardened to a plastic in the presence of oxygen, and he attributed this to the presence of a diastase in the lacquer. A few years later Bertrand (5) further purified this enzyme and named it laccase. He suggested that laccase is a metalloprotein containing manganese and introduced the term oxidase. About 50 years later Keilin and Mann (6) demonstrated that laccase is a copper enzyme and showed that its blue color disappears reversibly upon addition of substrate. Laccase has been extensively reviewed by the researchers in this field over the last 20 years, and a representative selection is listed (3, 7-12). 

The roles of the copper enzymes in electron transport, oxygen transport, and oxidation reactions have guaranteed continued interest in their study. In addition to studies of the natural compounds, there have been many attempts to design model structures of these enzymes, particularly of the binuclear species. Many of these include both nitrogen and oxygen donors built into macrocyclic ligands, although sulfur has been used as well. ... 

Copper enzymes are involved in reactions with a large number of other, mostly inorganic, substrates. In addition to its role in oxygen and superoxide activation described above, copper is also involved in enzymes which activate methane, nitrite, and nitrous oxide. 

Related to copper-containing enzymes such as laccase and tyrosinase, recent studies have been conducted on the structural characterization of the reactive species generated from molecular oxygen and copper complexes. A continuous effort has also been directed toward the efficient utilization of such oxygen-copper complexes as oxidants, in industrial processes, which will hopefully replace metal compounds such as chromate, manganate and others. 

Oxygen binding, activation, and reduction constitute processes carried out by copper enzymes. Solomon reported spectroscopic and... 

The occurrence, functions, and reactions catalyzed by copper enzymes indicate that copper only became biologically relevant after oxygen began to accumulate in the atmosphere. 

In all reactions catalyzed by copper enzymes, oxygen either functions as a substrate or as an electron-acceptor. 

Although there are flavin-dependent as well as copper-dependent amine oxidases, this section will only deal with the copper enzymes. Amine oxidase (EC 1.4.3.6) catalyzes the oxidative reaction of amines to aldehydes and ammonia. The two-step process generates two electrons which are utilized to reduce oxygen to hydrogen peroxide (H202) [28,113] ... 

A third category of copper enzymes are monooxygenases which, in addition to reducing O2 to H2O, add oxygen to the substrate. For example dopamine-j8-hydrox-ylase hydroxylates the benzylic position of dopamine (LIV) to give noradrenalin, one... 

---