Catalytic mechanism of the topa quinone containing copper amine oxidases
Catalytic mechanism of the topa quinone containing copper amine oxidases
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DOI：
10.1021/bi020246b
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发表时间：
2002-07-30
期刊：
影响因子：
2.9
通讯作者：
Klinman, JP
中科院分区：
文献类型：
--
作者：
Mure, M;Mills, SA;Klinman, JP
铜胺氧化酶 (CAO) 中 2, 4, 5-三羟基苯丙氨酸醌或托帕醌 [TPQ (1)] 1 的发现定义了一类新的酶促氧化还原辅助因子，其源自酪氨酸或色氨酸蛋白质侧链的翻译后修饰以形成醌类结构。图1A显示了已表征的辅因子的结构，即TPQ、赖氨酸酪氨酰醌[LTQ，通过酪氨酸和赖氨酸侧链交联形成(2)]、色氨酸色氨酸醌[TTQ，通过两个色氨酸侧链交联形成(3)]和半胱氨酸色氨酸醌[CTQ，通过半胱氨酸和色氨酸侧链的交联(4)]。研究表明，CAO 中的 TPQ 形成是通过铜离子依赖性自动氧化进行的，无需其他酶 (5, 6)。 TPQ 生物发生机制的细节不如催化转化机制那么明确，但它是一个活跃的研究领域（参见参考文献 7 和 8）。在本综述中，我们重点关注 TPQ 在底物（伯胺和分子氧）分别转化为醛和过氧化氢中的作用。由于 TPQ 酶的动力学表现出经典的乒乓机制 (9)，因此相对容易检查涉及底物胺氧化（还原半反应，方程式 1）和双氧还原（氧化半反应，方程式 2）的每个半反应：
The discovery of 2, 4, 5-trihydoxyphenylalanine quinone, or topaquinone [TPQ (1)] 1 in copper amine oxidases (CAOs) defined a new class of enzymatic redox cofactors derived from the post-translational modification of tyrosine or tryptophan protein side chains to form quinonoid structures. Figure 1A shows the structures of the cofactors which have been characterized, namely, TPQ, lysine tyrosyl quinone [LTQ, formed via the cross-linking of a tyrosine and a lysine side chain (2)], tryptophan tryptophyl quinone [TTQ, formed via the cross-linking of two tryptophan side chains (3)], and cysteine tryptophyl quinone [CTQ, formed via the crosslinking of a cysteine and a tryptophan side chain (4)]. It has been shown that TPQ formation in CAOs proceeds through a copper-ion-dependent autoxidation which does not require another enzyme (5, 6). The details of the mechanism of TPQ biogenesis are less well established than those for catalytic turnover and are an active area of investigation (cf. refs 7 and 8). In the present review, we focus on the increasingly well-described role for TPQ in the conversion of the substrates, primary amines and molecular oxygen, to aldehydes and hydrogen peroxide, respectively. Since the kinetics of the TPQ enzymes display a classical ping pong mechanism (9), it is relatively easy to examine each of the half reactions involving substrate amine oxidation (reductive half reaction, eq 1) and dioxygen reduction (oxidative half reaction, eq 2):