Traore Ephrahime S, Liu Aimin
Department of Chemistry, The University of Texas at San Antonio, San Antonio, Texas 78249, United States.
ACS Catal. 2022 May 20;12(10):6191-6208. doi: 10.1021/acscatal.1c04770. Epub 2022 May 10.
Here, the choice of the first coordination shell of the metal center is analyzed from the perspective of charge maintenance in a binary enzyme-substrate complex and an O-bound ternary complex in the nonheme iron oxygenases. Comparing homogentisate 1,2-dioxygenase and gentisate dioxygenase highlights the significance of charge maintenance after substrate binding as an important factor that drives the reaction coordinate. We then extend the charge analysis to several common types of nonheme iron oxygenases containing either a 2-His-1-carboxylate facial triad or a 3-His or 4-His ligand motif, including extradiol and intradiol ring-cleavage dioxygenases, thiol dioxygenases, -ketoglutarate-dependent oxygenases, and carotenoid cleavage oxygenases. After forming the productive enzyme-substrate complex, the overall charge of the iron complex at the 0, +1, or +2 state is maintained in the remaining catalytic steps. Hence, maintaining a constant charge is crucial to promote the reaction of the iron center beginning from the formation of the Michaelis or ternary complex. The charge compensation to the iron ion is tuned not only by protein-derived carboxylate ligands but also by substrates. Overall, these analyses indicate that charge maintenance at the iron center is significant when all the necessary components form a productive complex. This charge maintenance concept may apply to most oxygen-activating metalloenzymes systems that do not draw electrons and protons step-by-step from a separate reactant, such as NADH, via a reductase. The charge maintenance perception may also be useful in proposing catalytic pathways or designing prototypical reactions using artificial or engineered enzymes for biotechnological applications.
在此，从非血红素铁加氧酶中二元酶 - 底物复合物和氧结合三元复合物中的电荷维持角度，分析了金属中心第一配位层的选择。比较尿黑酸1,2 - 双加氧酶和龙胆酸双加氧酶，突出了底物结合后电荷维持作为驱动反应坐标的重要因素的意义。然后，我们将电荷分析扩展到几种常见类型的非血红素铁加氧酶，这些酶含有2 - 组氨酸 - 1 - 羧酸盐面三联体或3 - 组氨酸或4 - 组氨酸配体基序，包括二醇裂解和内二醇裂解双加氧酶、硫醇双加氧酶、α - 酮戊二酸依赖性加氧酶和类胡萝卜素裂解加氧酶。形成有效的酶 - 底物复合物后，处于0、+1或 +2状态的铁复合物的总电荷在其余催化步骤中得以维持。因此，保持恒定电荷对于促进从米氏复合物或三元复合物形成开始的铁中心反应至关重要。对铁离子的电荷补偿不仅由蛋白质衍生的羧酸盐配体调节，还由底物调节。总体而言，这些分析表明，当所有必要成分形成有效复合物时，铁中心的电荷维持很重要。这种电荷维持概念可能适用于大多数不通过还原酶从单独反应物（如NADH）逐步获取电子和质子的氧激活金属酶系统。电荷维持观念在提出催化途径或使用人工或工程酶设计用于生物技术应用的典型反应方面也可能有用。
