Klema Valerie J, Wilmot Carrie M
Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, 6-155 Jackson Hall, 321 Church St. SE, Minneapolis, MN 55455, USA.
Int J Mol Sci. 2012;13(5):5375-5405. doi: 10.3390/ijms13055375. Epub 2012 May 3.
Copper amine oxidases (CAOs) are a ubiquitous group of enzymes that catalyze the conversion of primary amines to aldehydes coupled to the reduction of O(2) to H(2)O(2). These enzymes utilize a wide range of substrates from methylamine to polypeptides. Changes in CAO activity are correlated with a variety of human diseases, including diabetes mellitus, Alzheimer's disease, and inflammatory disorders. CAOs contain a cofactor, 2,4,5-trihydroxyphenylalanine quinone (TPQ), that is required for catalytic activity and synthesized through the post-translational modification of a tyrosine residue within the CAO polypeptide. TPQ generation is a self-processing event only requiring the addition of oxygen and Cu(II) to the apoCAO. Thus, the CAO active site supports two very different reactions: TPQ synthesis, and the two electron oxidation of primary amines. Crystal structures are available from bacterial through to human sources, and have given insight into substrate preference, stereospecificity, and structural changes during biogenesis and catalysis. In particular both these processes have been studied in crystallo through the addition of native substrates. These latter studies enable intermediates during physiological turnover to be directly visualized, and demonstrate the power of this relatively recent development in protein crystallography.
铜胺氧化酶（CAOs）是一类普遍存在的酶，可催化伯胺转化为醛，并伴随将O₂还原为H₂O₂。这些酶利用从甲胺到多肽的多种底物。CAO活性的变化与多种人类疾病相关，包括糖尿病、阿尔茨海默病和炎症性疾病。CAOs含有一种辅因子，2,4,5-三羟基苯丙氨酸醌（TPQ），它是催化活性所必需的，通过CAO多肽内酪氨酸残基的翻译后修饰合成。TPQ的生成是一个自我加工过程，仅需向脱辅基CAO添加氧气和Cu(II)。因此，CAO活性位点支持两种截然不同的反应：TPQ合成以及伯胺的双电子氧化。从细菌到人类来源的晶体结构均已可得，这为了解底物偏好、立体特异性以及生物合成和催化过程中的结构变化提供了线索。特别是通过添加天然底物，在晶体中对这两个过程都进行了研究。这些后续研究能够直接观察到生理周转过程中的中间体，并证明了蛋白质晶体学这一相对较新进展的强大作用。
