| dc.description.abstract | Pseudomonas aeruginosa is an opportunistic, Gram negative, bacterial pathogen
that commonly establishes infection in immunocompromised individuals. It contains
protein-based, iron uptake pathways that target both heme and nonheme iron sources in the
host. When the Pseudomonas heme uptake system is compromised by genetic knockout of
the cytoplasmic heme trafficking protein, PhuS, the ability to establish infection is lost.
PhuS functions to transfer heme to a heme oxygenase, an 02 dependent heme metabolizing
enzyme, so that it can be degraded to a usable form for the organism. Within the long-term
goal of developing pharmaceutical agents to inhibit heme uptake by bacterial pathogens,
this study aims to evaluate the general thermodynamic parameters of metalloporphyrin
binding to PhuS. Two synthetic iron porphyrinates and the Ni(II) complex of
protoporphyrin IX have been investigated and their binding constants have been
determined. The implications of these results for inhibiting heme uptake will be discussed. | en_US |
