Protein hosts, transition metals

Transition metal complexes of phthalocyanine encaged in faujasite type zeolites have been reported as efficient catalysts in the oxidation of alkanes at room temperature and atmospheric pressure [6-13]. These catalysts constitute potential inorganic mimics of remarkable enzymes such as monooxygenase cytochrome P-450 which displays the ultimate in substrate selectivity. In these enzymes the active site is the metal ion and the protein orientates the incoming substrate relative to the active metal center. Zeolites can be used as host lattices of metal complexes [14, 15]. The cavities of the aluminosilicate framework can replace the protein terciary structure of natural enzymes, thus sieving and orientating the substrate in its approach to the active site. Such catalysts are constructed by the so-called ship in a bottle synthesis the metal phthalocyanine complexes are synthesized in situ within the supercages of the zeolite... 

Transition metal cofactors typically lose function when extracted from their host proteins. Related to this observation is the diminished, divergent, or nonexistent function of synthetic complexes modeled on metalloprotein active sites. Common to both of these phenomena is the loss of the tuning afforded by the protein matrix. The protein matrix surrounding such sites plays a vital role in the bioinorganic chemistry. 

There are three ways to introduce an appropriate transition metal center into a host protein, which can be an enzyme or a protein having no catalytic function (Fig. 4) ... 

Direct interaction of a transition metal salt with a designed binding site composed of appropriate amino acid side-chains in a host protein (Reetz et al., unpublished results). 

Fig. 4 Three strategies for introducing transition metals (M) site-spedfically in protein hosts...

This work demonstrates for the first time that it is possible to apply the methods of directed evolution to increase and/or to invert enantioselectivity of a hybrid catalyst composed of a synthetic achiral transition metal catalyst anchored to a host protein [130]. Due to the technical problems associated with the inefficient expression system, only very small mutant libraries could be generated, which in itself was labor-intensive. Nevertheless, proof-of-principle has been provided [130],... 

As mentioned above, Zn is the most abundant transition metal in cells, and plays a vital role in the functionalities of more than 300 enzymes, in the stabilization of DNA, and in gene expression. Other trace metals, such as Se, W, and Mo, are essential in human health and also important in the environment. For example, Se is usually incorporated into antioxidant enzymes as seleno-cysteine (SeCys), the redox active site of SeCys-containing enzymes, and plays a key role in host oxidative defense. It is predicted that there are a total of 25 SeCys-containing proteins in humans. The most widely known SeCys-containing enzymes are thioredoxin reductase and glutathione peroxidase. Both are ubiquitous and found in bacteria, plants, and mammals, including humans. ... 

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