Insights into the ubiquinol/dioxygen binding and proton relay pathways of the alternative oxidase
Insights into the ubiquinol/dioxygen binding and proton relay pathways of the alternative oxidase
复制标题
DOI：
10.1016/j.bbabio.2019.03.008
复制
发表时间：
2019-05-01
影响因子：
4.3
通讯作者：
Kita, Kiyoshi
中科院分区：
文献类型：
--
作者：
Shiba, Tomoo;Inaoka, Daniel Ken;Kita, Kiyoshi
交替氧化酶（AOX）是一种单位二铁羧酸盐蛋白，催化泛醇将分子氧还原为水。虽然我们最近已经确定了在存在和不存在子囊呋喃酮（AF）衍生物（这是有效的混合型抑制剂）的情况下，布氏锥虫AOX（TAO）的晶体结构的泛醇和双氧结合TAO的机制仍然没有定论。在这篇文章中，阿魏烯醇被确定为第一个竞争性抑制剂的AOX已被用来探测泛醇的结合。表面等离子体共振显示AF是TAO的准不可逆抑制剂，而阿魏烯醇结合是完全可逆的。在2.7埃下测定的TAO-阿魏烯醇复合物的结构提供了对泛醇结合的深入了解，并且还首次确定了以侧构象与二铁中心结合的潜在二氧分子。
The alternative oxidase (AOX) is a monotopic diiron carboxylate protein which catalyzes the four-electron reduction of dioxygen to water by ubiquinol. Although we have recently determined the crystal structure of Trypanosome brucei AOX (TAO) in the presence and absence of ascofuranone (AF) derivatives (which are potent mixed type inhibitors) the mechanism by which ubiquinol and dioxygen binds to TAO remain inconclusive. In this article, ferulenol was identified as the first competitive inhibitor of AOX which has been used to probe the binding of ubiquinol. Surface plasmon resonance reveals that AF is a quasi-irreversible inhibitor of TAO whilst ferulenol binding is completely reversible. The structure of the TAO-ferulenol complex, determined at 2.7 angstrom, provided insights into ubiquinol binding and has also identified a potential dioxygen molecule bound in a side-on conformation to the diiron center for the first time.