Conformational effects on flavin redox chemistry
Conformational effects on flavin redox chemistry
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DOI：
10.1021/jo9703865
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发表时间：
1997-08-08
影响因子：
3.6
通讯作者：
Rizzo, CJ
中科院分区：
文献类型：
--
作者：
Hasford, JJ;Kemnitzer, W;Rizzo, CJ
埃文斯和尼尔森表明，环状肼和联二酮的特定构象对其电子转移化学具有可测量的影响。 1 这种氧化还原电位的构象控制可能与酶促电子转移反应特别相关，因为氧化还原辅助因子的氧化形式和还原形式通常具有不同的几何形状；一个引人注目的例子是核黄素（1a，图 1）。 2 以 2.0 Å 分辨率解析了氧化型和还原型老黄酶的晶体结构，显示氧化型 FMN 辅因子的几何形状是平面的，而 1, 5-二氢FMN 则沿 N5、N10 轴弯曲（图 2）。 3 这些几何形状符合理论研究。 4 Massey 和 Hemmerich 提出，脱辅基酶可以通过控制构象来“调节”辅因子的氧化还原电位。 5 一些黄素酶的 X 射线晶体分析表明这可能是一个因素。例如，黄素氧还蛋白的蛋白质晶体结构显示，在所有三种氧化态下，辅因子的几何形状几乎都是平面的。 6 或者，三甲胺脱氢酶的氧化 FMN 辅因子沿 N5rN10 轴弯曲，并且与 1, 5-二氢黄素的构象非常相似。 7 我们合成了一系列构象偏向的黄素模型 (2r5)，以确定构象对黄素氧化还原性质的作用。我们使用 10-甲基异咯嗪 (2) 作为参考，因为它不会偏向氧化或还原形式。与 2, 9, 10-二甲基异咯嗪 (3) 相比，应显示出对还原态的偏好，因为相应 1, 5-二氢黄素的弯曲几何形状将减轻两个甲基取代基之间的空间相互作用；这可以在图 3 中的 Chem 3-D 表示中容易地看出。另一方面，对于 9、10 桥联黄素 4 和 5 的还原，N10 取代基不能从赤道位置转移到轴向位置，因为这会给束缚碳链带来扭转应变，因此，桥联黄素应该表现出对氧化态的偏好。模型黄素是通过所需的 N-烷基邻苯二胺与
Evans and Nelsen showed that the specific conformation of cyclic hydrazines and bianthrones had measurable effects on their electron-transfer chemistry. 1 Such conformational control of redox potentials could be particularly relevant in enzymatic electron-transfer reactions since the oxidized and reduced forms of redox cofactors often have different geometries; one dramatic example is riboflavin (1a, Figure 1). 2 The crystal structure of oxidized and reduced old yellow enzyme was solved at 2.0 Å resolution and showed the geometry of the oxidized FMN cofactor to be planar, while 1, 5-dihydroFMN is bent along the N5, N10 axis (Figure 2). 3 These geometries are in accord with theoretical studies. 4 Massey and Hemmerich proposed that the apoenzyme may “tune” the redox potential of the cofactor though control of conformation. 5 X-ray crystallographic analysis of some flavoenzymes suggest this may be a factor. For instance, the protein crystal structure of flavodoxin showed the cofactor’s geometry to be nearly planar in all three oxidation states. 6 Alternatively, the oxidized FMN cofactor of trimethylamine dehydrogenase is bent along the N5rN10 axis and strongly resembles the conformation of 1, 5-dihydroflavin. 7 We have synthesized a series of conformationally biased flavin models (2r5) to determine the role of conformation on the redox properties of flavins.We used 10-methylisoalloxazine (2) as a reference since it will not be biased toward the oxidized or reduced form. When compared to 2, 9, 10-dimethylisoalloxazine (3) should show a preference for the reduced state, since the bent geometry of the corresponding 1, 5-dihydroflavin will alleviate steric interaction between the two methyl substituents; this can be readily seen in the Chem 3-D representations in Figure 3. On the other hand, for the reduction of 9, 10-bridged flavins 4 and 5, the N10 substituent cannot shift from an equatorial to an axial position since this will impart torsional strain into the tethering carbon chain, and thus, the bridged flavins should show a preference for the oxidized state. The model flavins were synthesized by the condensation of the required N-alkyl-o-phenylenediamine with