Date of Award

Spring 1994

Document Type

Dissertation - Restricted

Degree Name

Doctor of Philosophy (PhD)



First Advisor

Wilkie, Charles

Second Advisor

Ryan, Michael

Third Advisor

Steinmetz, Mark


Heme proteins are a class of biological molecules that contain iron-porphyrin derivatives as prosthetic groups. Many of these heme proteins share the same naturally occurring protoporphyrin-IX (Figure 1.1) as the heme cofactor, and yet they vary dramatically in their specific biological functions. These functions include storage and transport of molecular oxygen (myoglobin and hemoglobin), catalysis of a wide range of complex reactions like hydroxylation of substrate (cytochrome P450), oxidation of organic and inorganic substrates using hydrogen peroxide as an oxidant (peroxidases), and disproportionation of hazardous species like H20 2 (catalases). In these proteins, the surrounding polypeptide chains vary considerably and ultimately determine the specificity and the function of the protein. Considerable effort over the last three decades has been devoted to elucidate the structural differences that lead to the functional diversity of these proteins. Three major factors appear to dictate the function of the protein (1): (i) the oxidation state of the iron center, (ii) the structure, geometry and the nature of axial ligand(s) attached to this complex, and (iii) the immediate environment of the complex, including polarity and steric effects that determine the accessibility of the substrate to the metal center. While hemoglobin, myoglobin and cytochrome P450 are biologically active in their ferrous state, peroxidases and catalases are active in their ferric states. The crystal structures of three of these proteins also show a wide variation in the nature of the fifth ligand coordinated to the metal center; Cytochrome c peroxidase (2,3) possessing an imidazole group of histidine, cytochrome P450 (4) having sulfur of cysteine and a number of catalases (5) contain a phenolate oxygen of a tyrosine residue...



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