Metallo-enzyme

Inspired by the many hydrolytically-active metallo enzymes encountered in nature, extensive studies have been performed on so-called metallo micelles. These investigations usually focus on mixed micelles of a common surfactant together with a special chelating surfactant that exhibits a high affinity for transition-metal ions. These aggregates can have remarkable catalytic effects on the hydrolysis of activated carboxylic acid esters, phosphate esters and amides. In these reactions the exact role of the metal ion is not clear and may vary from one system to another. However, there are strong indications that the major function of the metal ion is the coordination of hydroxide anion in the Stem region of the micelle where it is in the proximity of the micelle-bound substrate. The first report of catalysis of a hydrolysis reaction by me tall omi cell es stems from 1978. In the years that... 

Carbonic anhydrase was the first Zn metallo-enzyme to be discovered (1940) and in its several forms is widely distributed in plants and animals. It catalyses the equilibrium reaction ... 

Uncovering of the three dimentional structure of catalytic groups at the active site of an enzyme allows to theorize the catalytic mechanism, and the theory accelerates the designing of model systems. Examples of such enzymes are zinc ion containing carboxypeptidase A 1-5) and carbonic anhydrase6-11. There are many other zinc enzymes with a variety of catalytic functions. For example, alcohol dehydrogenase is also a zinc enzyme and the subject of intensive model studies. However, the topics of this review will be confined to the model studies of the former hydrolytic metallo-enzymes. 

Metallo-enzymes belonging to group 3 naturally show a very broad substrate spectrum including all (3-lactams excqrt monobactams and are not inhibited by clavulanic acid, but by complexing agents, like EDTA. This can only be exploited for diagnostic purposes. 

Antibiotic Resistance. Figure 1 According to Bush, Jacoby and Medeiros [2] four molecular classes of (3-lactamases can be discriminated based upon biochemical and molecular features. Classes 1, 2, and 4 included serine-proteases, while metallo enzymes are included in class 3. The substrate spectrum varies between different subclasses and the corresponding genes can be part of an R-plasmid leading to a wider distribution or are encoded chromosomally in cells of specific species. 

Industrial applications inclnde the production of petrochemicals, fine chemicals and pharmacenticals (particnlarly throngh asymmetric catalysis), hydrometallurgy, and waste-treatment processes. Many life processes are based on metallo-enzyme systems that catalyse redox and acid-base reactions. 

Catalysis by metal complexes is an exciting, fast developing and challenging interdisciplinary topic which spans and embraces the three areas of catalysis heterogeneons, homogeneons, and metallo-enzyme. 

Cohen, I. A. Metal-Metal Interactions in Metalloporphyrins, Metalloproteins and Metallo-enzymes. Vol. 40, pp. 1-37. 

Stanton and Merz studied the reaction of carbon dioxide addition to zinc hydroxide, as a model for zinc metallo-enzyme human carbonic anhydrase IIJ 36. It was shown that the LDA calculations (DFT(SVWN)) were not reliable for locating transition state structures whereas the post-LDA ones (DFT(B88/P86)) led to the transition state structures and ener-... 

The general metabolism of sulfur, extensively described in many texts of biological sciences, is not considered in this article some topics (e.g. metallo-enzymes) are discussed elsewhere in this volume (Chapter 11.2). Our focus is on sulfur-containing secondary metabolites in microorganisms and plants. In view of the vast literature, we can only provide an eclectic account citing recent work where possible. 

Ribozymes are a class of metallo-enzymes based on RNA rather than proteins. They have potential in clinical medicine, for example, as potential anti-HIV agents (568, 569) and as possible new tools for the treatment of cancer (570). The active structures of ribozymes contain domains of stacked helices which pack together through tertiary contacts. Divalent metal ions such as Mg(II), Zn(II), and Mn(II) can tune the reactivity and shape the structures of ribozymes (571). Manganese(II) and Mg(II) have similar hexacoordinate ionic radii (0.86 and 0.97 A, respectively) (572) and octahedral geometry ( )Ka of hydrates Ca(II), 12.7 Mg(II), 11.4 Mn(II), 10.7 Zn2+, 9.6) (571). There are several potential oxygen donors on the ribose sugar moiety. 

A different concept of chiral recognition was used by Lehn et al. (1978) for the differentiation between pairs of enantiomeric anions. Following the terminology used for metallo-enzymes, the chiral crown ether [309] acts as an apo-receptor, complexing a metal cation and thus becoming a chiral metal receptor that may discriminate between enantiomeric anions (cascade-type complexation). Extraction experiments with racemic mandelic acid dissolved in... 

The number of molecules with single electron orbitals, and therefore suitable for ESR, is limited due to the electron-sharing feature of the usual covalent bond. This tends to restrict its use to compounds containing transition metals and reactions involving free radicals. However, this does make ESR very useful for monitoring reactions involving metallo-enzymes or free radicals. 

K. P. Brooks, E. A. Jones, B. D. Kim, E. G. Sander, Bovine Liver Dihydropyrimidine Amidohydrolase Purification, Properties, and Characterization as a Zinc Metallo-enzyme , Arch. Biochem. Biophys. 1983, 226, 469-483. 

Lactamases (EC 3.5.2.6) inactivate /3-lactam antibiotics by hydrolyzing the amide bond (Fig. 5.1, Pathway b). These enzymes are the most important ones in the bacterial defense against /3-lactam antibiotics [15]. On the basis of catalytic mechanism, /3-lactamases can be subdivided into two major groups, namely Zn2+-containing metalloproteins (class B), and active-serine enzymes, which are subdivided into classes A, C, and D based on their amino acid sequences (see Chapt. 2). The metallo-enzymes are produced by only a relatively small number of pathogenic strains, but represent a potential threat for the future. Indeed, they are able to hydrolyze efficiently carbape-nems, which generally escape the activity of the more common serine-/3-lac-tamases [16] [17]. At present, however, most of the resistance of bacteria to /3-lactam antibiotics is due to the activity of serine-/3-lactamases. These enzymes hydrolyze the /3-lactam moiety via an acyl-enzyme intermediate similar to that formed by transpeptidases. The difference in the catalytic pathways of the two enzymes is merely quantitative (Fig. 5.1, Pathways a and b). 

An alternative presentation of the mechanisms in (2.82)-(2.84) and (2.86)-(2.88) is shown in (2.91). This depiction is popular in the complex mechanisms encountered in metallo-enzyme chemistry. 

Keywords Ribozymes, In vitro selection. Nucleic acid libraries, Metallo enzymes, Aptamers. 

Laccase is perhaps the metallo-enzyme most widely used for this aim. Laccases are a family of multicopper ( blue copper ) oxidases widely distributed in nature Many laccases have fungal origin, while others are produced in plants. They contain four Cu(II) ions, and catalyse the one-electron oxidation of four molecules of a reducing substrate with the concomitant four-electron reduction of oxygen to water . In view of their low redox potential, which is in the range of 0.5-0.8 V vs. NHE depending on the fungal source laccases typically oxidize phenols (phenoloxidase activity) or anilines. 

Organo-metallic macromolecules Metallo-enzyme Zinc finger... 

The binding and activation of molecular oxygen is an important process in nature and is achieved with the help of metallo-enzymes, e.g. dicopper enzymes... 

The catalytic function of the metals in these multinuclear metallo-enzymes may be rather electrostatic and seems insensitive to the nature of the metal ions. 

Chem. Soc., 126, 14411-14418 Skander, M., Malan, C., Ivanova, A. and Ward, TR. (2005) Chemical optimization of artificial metaUoenzymes based on the biotin-avidin technology (S)-selective and solvent-tolerant hydrogenation catalysts via the introduction of chiral amino acid spacers. Chem. Commun., 4815-4817 Ward, TR. (2005) Artificial metallo-enzymes for enantioselective catalysis based on the noncovalent incorporation of organometallic moieties in a host protein. Chem.-Eur. J., 11, 3798-3804 Letondor, C. and Ward, TR. (2006) Artificial metaUoenzymes for enantioselective catalysis Recent advances. Chem. Bio. Chem., 7, 1845-1852. 

---