The distribution and mechanism of iodotyrosine deiodinase defied expectations.
The distribution and mechanism of iodotyrosine deiodinase defied expectations.
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DOI：
10.1016/j.abb.2017.07.019
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发表时间：
2017-10-15
影响因子：
3.9
通讯作者：
Rokita SE
中科院分区：
文献类型：
--
作者：
Sun Z;Su Q;Rokita SE
碘酪氨酸脱碘酶（IYD）是不寻常的，它依赖于黄素和能力，促进还原脱卤在有氧条件下。正如名称所暗示的那样，这种酶首先被发现催化碘代酪氨酸中的碘消除，以在统称为甲状腺激素的四碘甲状腺原氨酸和三碘甲状腺原氨酸的合成过程中回收碘。然而，IYD可能支持更多的功能，并已被证明可以使溴代和氯代酪氨酸脱溴和脱氯。卤代酪氨酸相对于卤代酚的特异性从人到细菌都得到了很好的保留。在迄今为止的所有实施例中，底物两性异恶唑啉与蛋白质和黄素的异咯嗪环都建立了极性接触。机理数据表明，脱卤催化的顺序一个电子转移步骤，从还原黄素基板，尽管最初的期望为一个单一的两个电子转移机制。一种假定的黄素半醌中间体通过其N5位和Thr侧链之间的氢键而稳定。该残基突变为Ala抑制脱卤并增强硝基还原酶活性，这使人联想到相同结构超家族内的其他酶。
Iodotyrosine deiodinase (IYD) is unusual for its reliance on flavin and ability 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.
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影响因子：
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影响因子：
3.2
作者：
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