Heme proteins, modification

K. Chattopadhyay and S. Mazumdar, Direct electrochemistry of heme proteins effect of electrode surface modification by neutral surfactants. Bioelectrochemistry 53, 17-24 (2000). 

In Ref. [279] the technique of protein modification was used to study the dependence of the rate of photoinduced electron tunneling on the distance between TZnP and Ru(III) sites in modified myoglobins. The modified proteins were prepared by substitution of zinc mesoporphyrin IX diacid for the heme in four various pentaammineruthenium (III) derivatives of sperm whale myoglobin (NH3)5Ru(His-48)Mb, (NH3)5Ru(His-12)Mb, (NH3)5Ru(His-116)Mb and (NH3)5Ru(His-81)Mb. Metal-to-metal distance between ZnP and (NH3)5Ru(His) ranges in this seria from 16.1-18.8 A for His-48 to 27.8-30,5 for His-12. The rate constant of electron tunneling decreases in this series in accordance with Eq. (1) with ve = 7.8 x 10s s 1 and ae = 2.2 A at T = 298 K. 

Chloramphenicol and secobarbital exhibit properties similar to those of tienilic acid, but they have not been studied in humans (11). Oxidative dechlorination of chloramphenicol with formation of reactive acyl chlorides appears to be an important metabolic pathway for irreversible inhibition of CYP. Chloramphenicol binds to CYP, and subsequent substrate hydroxylation and product release are not impaired. The inhibition of CYP oxidation and the inhibition of endogenous NADPH oxidase activity suggest that some modification of the CYP has taken place, which inhibits its ability to accept electrons from the CYP reductase (11). Secobarbital completely inactivates rat CYP2B1 functionally, with partial loss of the heme chromophore. Isolation of the N-alkylated secobarbital heme adduct and the modified CYP2B1 protein revealed that the metabolite partitioned between heme N-alkylation, CYP2B1 protein modification, and epoxidation. A small fraction of the prosthetic heme modifies the protein and contributes to the CYP2B1 inactivation (12). 

Huang LS, Ortiz de Montellano PR (2006) Heme-protein covalent bonds in peroxidases and resistance to heme modification during halide oxidation. Arch Biochem Biophys 446 77-83... 

Wojciechowski G, Huang L, Ortiz de Montellano PR (2005) Autocatalytic modification of the prosthetic heme of horseradish but not lactoperoxidase by thiocyanate oxidation products. A role for heme-protein covalent crosslinking. J Am Chem Soc 127 15871-15879... 

Regarding the chemical modification of the heme molecule located in the active site of peroxidases and other heme-proteins with peroxidase activity, a few examples are now discussed. Free carboxylic groups of heme from horse heart cytochrome c... 

A5. Alayash, A. I., Ryan, B. A., and Cashon, R. E., Peroxynitrite-mediated heme oxidation and protein modification of native and chemically modified hemoglobins. Arch. Biochem. Biophys. 349, 65-73 (1998). 

Keywords Absorptive capacity sorption efficiency erythrocyte toxicity test (osmotic) heme protein restored-iron iron-silica iron-carbon surface modification blood detoxification barbiturates bilirubin blood purification. 

Calcium-binding Proteins Copper Enzymes in Denitrification Copper Proteins with Type 1 Sites Copper Proteins with Type 2 Sites Iron Heme Proteins Electron Transport Iron-Sulfin Proteins Metal-mediated Protein Modification Metallochaperones Metal Ion Homeostasis Molybdenum MPT-containing Enzymes Nickel Enzymes Cofactors, Nitrogenase Catalysis Assembly Zinc Enzymes. 

Some of the spectral effects of specific covalent modifications of proteins, i.e., iodination, oxidation, tyrosinase action, etc., will be discussed briefly. Heme proteins, flavoproteins, and other conjugated proteins will not be discussed except as regards studies involving their amino acid components. 

Figure 42. The preparation of a photoenzyme by the reconstitution of a heme protein with Co(II)-protoporphyrin IX and the chemical modification of the protein backbone with a tethered chro-mophore. Hydrogen evolution and hydrogenation of acetylene derivatives photobiocatalyzed by the assembly.

Myriad metalloproteins bind iron-protoporphyrin IX, known as heme (Fig. 15). Heme protein properties are determined by a variety of factors within the inner coordination sphere and without. These include chemical modifications to the porphyrin macrocycle, different axial ligation, perturbations to conformation, and protein dynamics surrounding the cofactor. Because of the extensive proliferation of heme proteins, we will limit ourselves to a small subset. These will include the cytochromes c, myoglobins, heme oxygenases and peroxidases, and a heme-based chemical sensor. 

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