Sun Zuodong, Su Qi, Rokita Steven E
Department of Chemistry, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA.
Department of Chemistry, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA.
Arch Biochem Biophys. 2017 Oct 15;632:77-87. doi: 10.1016/j.abb.2017.07.019. Epub 2017 Jul 31.
Iodotyrosine deiodinase (IYD) is unusual for its reliance on flavin to promote reductive dehalogenation under aerobic conditions. As implied by the name, this enzyme was first discovered to catalyze iodide elimination from iodotyrosine for recycling iodide during synthesis of tetra- and triiodothyronine collectively known as thyroid hormone. However, IYD likely supports many more functions and has been shown to debrominate and dechlorinate bromo- and chlorotyrosines. A specificity for halotyrosines versus halophenols is well preserved from humans to bacteria. In all examples to date, the substrate zwitterion establishes polar contacts with both the protein and the isoalloxazine ring of flavin. Mechanistic data suggest dehalogenation is catalyzed by sequential one electron transfer steps from reduced flavin to substrate despite the initial expectations for a single two electron transfer mechanism. A purported flavin semiquinone intermediate is stabilized by hydrogen bonding between its N5 position and the side chain of a Thr. Mutation of this residue to Ala suppresses dehalogenation and enhances a nitroreductase activity that is reminiscent of other enzymes within the same structural superfamily.
碘酪氨酸脱碘酶（IYD）不同寻常之处在于，它在有氧条件下依赖黄素来促进还原性脱卤反应。顾名思义，这种酶最初被发现可催化碘酪氨酸的碘消除反应，以便在甲状腺激素（统称甲状腺激素，包括四碘甲状腺原氨酸和三碘甲状腺原氨酸）合成过程中回收碘。然而，IYD可能支持更多功能，并且已被证明可使溴酪氨酸和氯酪氨酸发生脱溴和脱氯反应。从人类到细菌，对卤代酪氨酸与卤代酚的特异性都得到了很好的保留。在迄今为止的所有实例中，底物两性离子与蛋白质以及黄素的异咯嗪环都形成了极性接触。机理数据表明，尽管最初预期为单一的双电子转移机制，但脱卤反应是由从还原型黄素到底物的连续单电子转移步骤催化的。一种所谓的黄素半醌中间体通过其N5位置与苏氨酸侧链之间的氢键得以稳定。将该残基突变为丙氨酸会抑制脱卤反应，并增强硝基还原酶活性，这让人联想到同一结构超家族中的其他酶。
