Metalloenzyme systems

Essential and Trace The discussion of metalloporphyrins and metalloenzymes systems has indicated the... 

A similar restriction in intramolecular energy flow has been postulated for metalloenzyme systems [41]. In particular, in the formation of the enzyme substrate complex, the energy of binding can be trapped at the metal active site. The... 

Recently, we have turned our attention to some co-oxidation reactions that are remarkably similar to a P-450 system (Reaction 1) in that hydride is used as the coreductant the H and H+ requirements of the metalloenzyme system are furnished in our systems by a metal that activates molecular H2 via heterolytic cleavage (97), Reaction 26... 

Table 1 Metalloenzyme systems discussed by Himo and Siegbahn [ 16] ...

This cross relationship is often applied to metalloenzyme systems to determine their self-exchange rates, because techniques are seldom available to measure the values directly. These applications have variable success and the difflculties usually are attributed to varying points of attack on the enzyme and induced conformational changes in the enzyme. 

Hydrogenation of A-acetamidoacrylate with the avidin-biotin and rhodium-diphosphine complexes shows a moderate enantioselectivity, yielding (S)-N-acetamidoalanine at41% ee (Figure 12.8). " Subsequently, an artificial metalloenzyme system using a combination of biotinylated diphosphine with mntated streptavidine was prepared. This catalytic system qnantitatively yielded highly enantioselective products ((R) = 94%). ... 

The plenary lectures at the 14th I.C.C.C. Meeting at Toronto have been published, as have the papers presented at the Bressanone Conference. Several other useful reviews of reactions involving metal ions have been published. The oxidation-reduction of the cobalt centre in vitamin Big has been discussed and recent developments in the bioinorganic chemistry of this complex have also been described. -Electron-transfer catalysts involving metalloenzyme systems have also been reviewed by Williams. The role of transition metals in homogeneous catalysis has been described and homo-lytic oxidation and reduction reactions of organic compounds by metallic ions have been reviewed. ... 

In this review, we will describe the model studies of hydrolytic metalloenzymes of the second category, emphasizing those of micellar systems. Here it should be mentioned that such micellar models have been studied only little in the past so that the major,part of this review bases on our own work. 

Several model systems related to metalloenzymes such as carboxypeptidase and carbonic anhydrase have been reviewed. Breslow contributed a great deal to this field. He showed how to design precise geometries of bis- or trisimidazole derivatives as in natural enzymes. He was able to synthesize a modified cyclodextrin having both a catalytic metal ion moiety and a substrate binding cavity (26). Murakami prepared a novel macrocyclic bisimidazole compound which has also a substrate binding cavity and imidazole ligands for metal ion complexation. Yet the catalytic activities of these model systems are by no means enzymic. 

Carbonic anhydrase (CA) exists in three known soluble forms in humans. All three isozymes (CA I, CA II, and CA III) are monomeric, zinc metalloenzymes with a molecular weight of approximately 29,000. The enzymes catalyze the reaction for the reversible hydration of C02. The CA I deficiency is known to cause renal tubular acidosis and nerve deafness. Deficiency of CA II produces osteopetrosis, renal tubular acidosis, and cerebral calcification. More than 40 CA II-defi-cient patients with a wide variety of ethnic origins have been reported. Both syndromes are autosomal recessive disorders. Enzymatic confirmation can be made by quantitating the CA I and CA II levels in red blood cells. Normally, CA I and CAII each contribute about 50% of the total activity, and the CAI activity is completely abolished by the addition of sodium iodide in the assay system (S22). The cDNA and genomic DNA for human CA I and II have been isolated and sequenced (B34, M33, V9). Structural gene mutations, such as missense mutation, nonsense... 

There has been considerable recent activity developing appropriate parameters to allow semi-empirical methods to describe a variety of biologically important systems, and their related properties, such as (i) enzyme reactivity, including both over- and through-barrier processes, (ii) conformations of flexible molecules such as carbohydrates, (iii) reactivity of metalloenzymes and (iv) the prediction of non-covalent interactions by addition of an empirical dispersive correction. In this review, we first outline our developing parameterisation strategy and then discuss progress that has been made in the areas outlined above. 

Type (820) dinickel complexes offer the opportunity of substrate binding within the bimetallic pocket, and highly preorganized complexes of this type have also been employed as model systems for the urease metalloenzyme (see Section 6.3.4.12.7). The Ni—Ni separation in type (820) complexes can be... 

The system illustrated by (272) forms the basis of a model for the zinc-containing metalloenzyme, carbonic anhydrase (Tabushi Kuroda, 1984). It contains Zn(n) bound to imidazole groups at the end of a hydrophobic pocket, as well as basic (amine) groups which are favourably placed to interact with a substrate carbon dioxide molecule. These are both features for the natural enzyme whose function is to catalyze the reversible hydration of carbon dioxide. The synthetic system is able to mimic the action of the enzyme (although side reactions also occur). Nevertheless, the formation of bicarbonate is still many orders of magnitude slower than occurs for the enzyme. 

Metal-sulfur aggregates are now known to occur in biological systems as the active sites of a significant number of metalloenzymes, and clarification of their detailed structures are currently progressing rapidly. In consideration of the results of these studies, many researchers are attempting to synthesize the direct structural models as well as the functional models of the active sites of natural enzymes that promote various important reactions in the biological systems under ambient conditions, which presumably leads in the near future to the... 

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