Studies of Cofactor Biogenesis in Copper Amine Oxidase

描述：(申请人提供)含铜胺氧化酶 (Cas)是催化氧化脱氨反应的一个不同的酶家族。 伯胺。在哺乳动物中，CAO的类别直接与 慢性糖尿病疾病和心力衰竭，使它们成为 药物调查。CAO是在最初不成熟的、 非活动形式。为了变得有功能，来自特定的酪氨酸侧链 活性中心残基必须转化为氧化还原活性辅因子， 2，4，5-三羟基苯丙烷酮(TPQ)。辅因子成熟过程 (称为生物发生)通过 酶，相对来说还未被开发。这份提案详细说明了四套 通过实验了解冠脉闭塞症中TPQ的生物发生机制 酵母菌(汉逊酵母)。具体地说，目标是：(1)表征 生物发生的中间体；(2)探索生物体的电子学特征 活性中心铜(II)；(3)阐明氧结合的位置；(4)定义 活性中心残基在生物发生中的作用。

DESCRIPTION: (provided by applicant) The copper-containing amine oxidases (CAOs) are a diverse family of enzymes which catalyze the oxidative deamination of primary amines. In mammals, classes of CAOs have been directly linked with chronic diabetic disorders and heart failure, making them a target for pharmaceutical investigation. CAOs are produced in an initially immature, inactive form. To become functional, a tyrosine sidechain from a specific active site residue must be converted into a redox-active cofactor, 2,4,5-trihydroxyphenylalaninequinone (TPQ). The process of cofactor maturation (referred to as biogenesis) occurs by a self-processing mechanism within the enzyme, and is relatively unexplored. This proposal details four sets of experiments aimed at understanding the TPQ biogenesis mechanism in a CAO from yeast (Hansenula polymorpha). Specifically, the goals are: (1) to characterize an intermediate in biogenesis; (2) to probe the electronic character of the active site Cu(II); (3) to elucidate a site of dioxygen binding; (4) to define roles of active site residues in biogenesis.