Metalloproteins, artificial

Watanabe and co-workers pursued an approach involving the non-covalent placement of Mn (III) and Cr (III) salophen complexes into apo-myoglobin [61]. In this artificial metalloprotein, two residues required mutation to improve the binding affinity of the... 

Carey JR, Ma SK, Pfister TD et al (2004) A site-selective dual anchoring strategy for artificial metalloprotein design. J Am Chem Soc 126 10812-10813... 

Covalent attachment has also been exploited for protein incorporation of non-native redox active cofactors. A photosensitive rhodium complex has been covalently attached to a cysteine near the heme of cytochrome c (67). The heme of these cytochrome c bioconjugates was photoreducible, which makes it possible for these artificial proteins to be potentially useful in electronic devices. The covalent anchoring, via a disulfide bond, of a redox active ferrocene cofactor has been demonstrated in the protein azurin (68). Not only did conjugation to the protein provide the cofactor with increased water stability and solubility, but it also provided, by means of mutagenesis, a means of tuning the reduction potential of the cofactor. The protein-aided transition of organometallic species into aqueous solution via increased solubility, stability and tuning are important benefits to the construction of artificial metalloproteins. 

Ueno T, Abe S, Yokoi N, Watanabe Y. Coordination design of artificial metalloproteins utilizing protein vacant space. Coord. Chem. Rev. 2007 251 2717-2731. 

Abe S, Ueno T, Reddy PAN, Okazaki S, Hikage T, Suzuki A, Yamane T, Nakajima H, Watanabe Y. Design and structure analysis of artificial metalloproteins selective coordination of His64 to copper complexes with square-planar structure in the apo-myoglobin scaffold. Inorg. Chem. 2007 46 5137-5139. Ohashi M, Koshiyama T, Ueno T, Yanase M, Fuji H, Watanabe Y. Preparation of artificial metalloenzymes by insertion of chromium Schiff base complexes into apomyoglobin mutants. Angew. Chem Int. Ed. 2003 42 1005-1008. 

Ueno T, Ohashi M, Kono M, Kondo K, Suzuki A, Yamane T, Watanabe Y. Crystal structures of artificial metalloproteins tight binding of Felll(Schiff-Base. by mutation of Ala71 to Gly in apo-myoglobin. Inorg. Chem. 2004 43 2852-2858. 

Artificial Metalloproteins Exploiting Vacant Space Preparation, Structures, and Functions... 

In this chapter, the key topics of artificial metalloproteins utilizing protein vacant space are reviewed, outhning recent studies since 2000. Section 3 shows the approaches for construction of the metal complex/protein composites and their crystal structures and, further, describes the interactions between metal-drugs and proteins. Section 4... 

Table 1 Summary of proteins and metal complexes for the preparation of artificial metalloproteins and their functions...

For the construction of artificial metalloproteins, protein scaffolds should be stable, both over a wide range of pH and organic solvents, and at high temperature. In addition, crystal structures of protein scaffolds are crucial for their rational design. The proteins reported so far for the conjugation of metal complexes are listed in Fig. 1. Lysozyme (Ly) is a small enzyme that catalyzes hydrolysis of polysaccharides and is well known as a protein easily crystallized (Fig. la). Thus, lysozyme has been used as a model protein for studying interactions between metal compounds and proteins [13,14,42,43]. For example, [Ru(p-cymene)] L [Mn(CO)3l, and cisplatin are regiospecificaUy coordinated to the N = atom of His 15 in hen egg white lysozyme [14, 42, 43]. Serum albumin (SA) is one of the most abundant blood proteins, and exhibits an ability to accommodate a variety of hydrophobic compounds such as fatty acids, bilirubin, and hemin (Fig. lb). Thus, SA has been used to bind several metal complexes such as Rh(acac)(CO)2, Fe- and Mn-corroles, and Cu-phthalocyanine and the composites applied to asymmetric catalytic reactions [20, 28-30]. 

Successful structural analyses of artificial metalloproteins have been reported [5, 6, 17, 22]. Hayashi et al. have determined the crystal structure of a reconstituted apo-Mb with the iron porphycene derivative 13,16-dicarboxyethyl-2,7-diethyl-3,6,12,17-tetramethylporphycenato-Fe " (iron porphycene) [22], The structure shows... 

Fig. 3 Crystal structures of active site of artificial metalloproteins a Fe(Porphycene) apo-Mb, and b Cr(Schiffbase) apo-A71G Mb taken from PDB ID 2D6C, and 1V9Q, respectively...

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