XAS STUDIES OF COPPER MONOOXYGENASE ENZYMES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。铜单加氧酶在神经和内分泌功能中起重要作用。肽酰甘氨酸a-酰胺化单氧合酶（PHM）和多巴胺b-单氧合酶（DBM）分别在神经肽激素和儿茶酚胺类神经递质的生物合成途径中占据关键位置。PHM的两种催化机制——基质介导的电子转移和超氧化物通道，在铜单氧反应中都是前所未有的。它们之间的差异在很大程度上集中在铜最初在完全还原状态下与二氧反应，以及晶体学确定的肽结合位点是否准确地描述了过渡状态。布莱克本实验室正在进行一项重大计划，以区分这两种机制。本提案中描述的XAS实验是本计划的重要组成部分。

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.