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. Copper monooxygenases play important roles in neurological and endocrine function. Two enzymes, peptidylglycine a-amidating monooxygenase (PHM) and dopamine b-monooxygenase (DBM) occupy key positions in the biosynthetic pathways to neuropeptide hormones and catecholamine neurotransmitters respectively. The two mechanisms proposed for the catalytic function of PHM, substrate-mediated electron transfer and superoxide channeling are each novel and unprecedented in copper monooxygenation reactions. The differences between them focus to a large extent on which copper initially reacts with dioxygen in the fully reduced state, and whether the crystallographically determined peptide binding site accurately describes the transition state. A major program is ongoing in the Blackburn laboratory to distinguish between the two mechanisms. The XAS experiments described in this proposal are an essential component of this program.
Showing the most recent 10 out of 604 publications
