Catalase HPII of Escherichia coli is similar in sequence and structure to other catalases including the conservation of several residues on both the distal and proximal sides of the active center heme. The roles of many residues on the distal side of the heme have been well characterized. By contrast, very few residues on the proximal side of the heme or in the plane of the heme have been investigated. The primary goal of this thesis is to develop a better understanding of the role of the residues and structural features at the core of catalases and in the lateral access channel. The results demonstrate that a break in molecular symmetry does not have any functional significance. Replacing Ile274 with a Cys resulted in the heme being covalently linked to the protein through a Cys-vinyl bond which is hypersensitive to X-ray irradiation being largely degraded within seconds of exposure to the X-ray beam.