HIGH RESOLUTION SAR STUDIES ON CAVITY MUTANTS OF CYTOCHROME C PEROXIDASE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Structure-affinity relationships (SAR) will be studied in a cavity mutant, W51A, of the heme enzyme, cytochrome c peroxidase (CCP). Single and mixed ligand solutions will be soaked into the hydrophobic CCP cavity and assignment of the bound ligand(s) will depend on the quality of the electron density which in turn is dependent on the specificity of the site for one particular ligand and one binding mode. Initial, in-house data has been collected on ligand soaks into this mutant, but the electron density lacks the detail necessary to distinguish the identity of certain atoms and their chirality. High resolution x-ray crystallography using synchrotron radiation will provide the detailed information required to correctly identify the different enantiomeric products soaked into CCP. These types of studies will further contribute to a better understanding of protein-ligand interactions which in turn will advance the fields of structure-based drug design and protein engineering.