Mutation myoglobin

Figure 3.13 The hemoglobin molecule is built up of four polypeptide chains two a chains and two (3 chains. Compare this with Figure 1.1 and note that for purposes of clarity parts of the a chains are not shown here. Each chain has a three-dimensional structure similar to that of myoglobin the globin fold. In sicklecell hemoglobin Glu 6 in the (3 chain is mutated to Val, thereby creating a hydrophobic patch on the surface of the molecule. The structure of hemoglobin was determined in 1968 to 2.8 A resolution in the laboratory of Max Perutz at the MRC Laboratory of Molecular Biology, Cambridge, UK.

One of the most significant common aspects of the chemistry of NO and peroxynitrite is their ability to react in a unique manner with the metal centers of numerous proteins, in particular hemoproteins [10]. We have used myoglobin (Mb) and hemoglobin (Hb) to investigate the diverse reactions that these simple inorganic biomolecules can undergo with different oxidation states of hemoproteins. Mutated forms of Mb and Hb are available [12, 13], and a large number of transition metals ions other than Fe ions have been successfully incorporated in these... 

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... 

To increase the enantioselectivity of these myoglobin metalloenzymes, Lu and co-workers have successfully utilized a covalent linkage approach [62], In an earlier attempt a Mn(III)-salen complex was incorporated into apo-myoglobin by mutating residue 103 to cysteine, followed by modification with a methane thiosulfonate derivative of Mn(III)(salen) (Figure 5.16). This catalyst showed sulfoxidation activity however, the ee was only 12 %. As such a low ee might be a result of the ability of the bound ligand to exist in multiple conformations within the protein cavity, it was hypothesized that the rotational freedom of the salen complex could be limited if it was anchored at... 

Figure 5.17 Structure of myoglobin complexed with a heme group. The two residues chosen for mutation, Y103 and L72, are shown. Left Side view of myoglobin. Right Top view of myoglobin. Color scheme Carbon (white), oxygen (red), nitrogen (blue), iron (pink).

Figure 35. Global mapping of surface hydration dynamics of apoMb. Shown is the X-ray crystal structure of sperm whale myoglobin (PDB ID 1MBD) in the holo form with eight helices A—H. In apo form, parts of the structure are melted and they are shown in transparent gray. The 16 balls indicate positions of mutation with tryptophan one at a time.

Ozaki S, Matsui T, Watanabe Y (1996) Conversion of myoglobin into a highly stereospecific peroxygenase by the L29FI/H64L mutation. J Am Chem Soc 118 9784-9785... 

Hayashi T, Hitomi Y, Ando T et al (1999) Peroxidase activity of myoglobin is enhanced by chemical mutation of heme-propionates. J Am Chem Soc 121 7747-7750... 

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