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|Title:||The Utilization of Metalloporphyrins as Mechanistic Probes of the Active Site of Heme Proteins|
|Author(s):||Reinert, Thomas Joseph|
|Department / Program:||Chemistry|
|Degree Granting Institution:||University of Illinois at Urbana-Champaign|
|Abstract:||Iron protoporphyrin-IX is a ubiquitous active site in biological systems. It provides the redox couple for electron transport, facilitates the insertion of an oxygen atom into an organic substrate, and also serves as the binding site for dioxygen in O$\sb2$ transport/storage hemoproteins. In the latter, one observes a range of 10$\sp5$ in O$\sb2$ affinities among heme proteins, discrimination in binding O$\sb2$ vs. CO, and cooperative ligand binding observed in hemoglobin.
This range of functions is regulated by the interactions between the heme and the protein. Two methods utilized to examine the structure/function relationship of the environment about the heme and the ligand affinity of the metal center are: (1) the synthesis and study of small molecule analogs of the active site; and (2) the effect of metal substitution in the heme.
Small molecule analogs of the active site allow the systematic variation of components of the model. Various CO and O$\sb2$ affinities have been determined on synthetic iron porphyrin systems. They have revealed: (1) the role of putative steric contacts between the porphyrin plane and the bound imidazole plays in the regulation of ligand affinity; the role hydrogen bonding to the bound imidazole exerts on the CO affinity of the metal center; and, a new mechanism for CO/O$\sb2$ discrimination dependent upon the polarity at the binding site.
Alternatively, substitution of the metal within the active site allows another method of probing the effect the protein environment has upon the metal center. The utilization of cobalt substituted hemoproteins to examine the nature of the bound dioxygen in hemoproteins is well-established. The affinity data (both thermodynamic and kinetic) obtained from cobalt myoglobin and cobalt leghemoglobin when compared with the data for the native systems has revealed an explanation for the high dioxygen affinity of leghemoglobin.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1987.
|Date Available in IDEALS:||2014-12-15|