Binuclear metalloenzymes

The cyclooctapyrroles shown in Figure 55 appear predestined to form binuclear metal complexes since the loop-shaped conformation of these macrocycles exhibits two structurally identical, helical N4 cavities. Enantiomers of such complexes, which are presumably generally very stable towards racemization owing to the rigidity of the molecule imposed by the incorporation of the metal, are of interest as possible models for binuclear metalloenzymes and as potential catalysts in asymmetric synthesis. The first two ligands as well as their recently obtained palladium complexes601 were... 

DapE has significant sequence homology with ArgE, CPG, and ACYl, all binuclear enzymes that are members of the zinc a,/3-hydrolase superfamily, but this enzyme contains only one bound zinc ion as isolated. " Treatment with a metal chelator (EDTA) decreases the observed activity, whereas the addition of Zn or Co to the purified enzyme enhances catalytic activity. " " The activity ( cat/- M) follows the order ZnCo > ZnZn > CoCo > CoZn, Zn, Co, " suggesting that DapE functions as a binuclear metalloenzyme. 

Selected examples of matrix-confined structural and spectroscopic models of mono- and binuclear metalloenzymes will be highlighted in the following paragraphs, in addition to aspects of the synthesis, characterization, and special properties. 

Binuclear metalloenzymes are prevalent in nature, performing a range of functions on various substrates. Dicopper sites have an important role in flie activation of biological oxygen, and the study of structural and functional aspects of copper metalloenzymes via model systems is a subject of intense research. One member of the family of dicopper proteins is catechol oxidase, which features a type 3 copper... 

Kinetic evidence obtained for intramolecular proton transfer between nickel and coordinated thiolate, in a tetrahedral complex containing the bulky triphos ligand (Pl PCE CE PPh to prevent interference from binuclear p-thiolate species, is important with respect to the mechanisms of action of a number of metalloenzymes, of nickel (cf. urease, Section VII. B.4) and of other metals (289). 

The preparation and characterization of novel man-ganese(III) complexes of various porphyrin and porphyrin-likes macrocycles have continued to attract strong attention especially because of their importance in catalytical oxidation processes through the formation of a Mn(V)0 intermediate (see Section 6) and as model for metalloenzymes. In this line, an artificial enzyme formed through a directed assembly of a molecular square that encapsulated a Mn porphyrin has been prepared and investigated as a catalyst. In contrast to symmetrical binuclear bis(phenoxo) bridged macrocyclic Mn(III)Mn(III) complexes, unsymmetrical ones are rare. A new series of these kinds of carboxylate-free complexes has been described and their redox properties investigated. ... 

Tyrosinase (see Copper Proteins with Dinuclear Active Sites), a copper metalloenzyme with a very broad phylogenetic distribution, is responsible for the browning of fruits and mushrooms.Tyrosinase is a bifimctional phenol oxidase that is able to both hydroxylate monophenols like tyrosine (monooxygenase reaction, (equations)) and snbseqnently oxidize the diphenol product to the corresponding quinone (oxidase reaction, (equation 6)) at a single Type 3 binuclear copper active site. 

Arginase A Binuclear Manganese Metalloenzyme David E. Ash, J. David Cox, and David Wi Christianson... 

N-Hydroxyamino acids, similar in action to N-hydroxyurea, some N-hydroxyamides and some aromatic hydroxy acids, are inhibitors of ribonucleotide reductases 112), a unique group of metalloenzymes, essential for cell proliferation. Inhibition of substrate reduction in vitro (l5o = 2.3-10 ) is accompanied by decay of the tyrosyl radical but not the iron atom from the E. coli subunit B2 of this enzyme. Inhibitors of the above type donate an electron to the enzyme s free radical, producing an inactive protein-enzyme with a still intact binuclear iron complex and a new more stable free radical of the nitroxide type (52)... 

Hies, M., Di Costanzo, L.D., North, M.L., Scott, J.A., and Christianson, D.W. (2010) 2-Aminoimidazole amino acids as inhibitors of the binuclear manganese metalloenzyme human arginase I. J. Med. Chem., 53, 4266A276. 

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