The minimal structure for iodotyrosine deiodinase function is defined by an outlier protein from the thermophilic bacterium Thermotoga neapolitana.
The minimal structure for iodotyrosine deiodinase function is defined by an outlier protein from the thermophilic bacterium Thermotoga neapolitana.
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DOI：
10.1016/j.jbc.2021.101385
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Rokita SE
中科院分区：
文献类型：
--
作者：
Sun Z;Xu B;Spisak S;Kavran JM;Rokita SE
硝基还原酶超家族的酶包括许多黄素单核苷酸（FMN）依赖的催化剂促进广泛的反应。它们都有一个共同的核心，由一个fmn结合域组成，每个亚群还包含一到三个序列延伸，从核心内的指定位置辐射，以支持它们独特的催化性能。为了确定这个超家族中碘酪氨酸脱碘酶亚群的活性所需的最小结构，研究人员将注意力集中在嗜热生物热袍（Thermotoga neapolitana, TnIYD）的代表上。这个代表是根据它作为亚群的一个异常值的地位被选中的，这是由于它在所有嗜中菌同源物中都缺乏某些明显的标准基序。我们发现，TnIYD缺乏一个典型的n端序列及其两个特征序列扩展之一，这两个序列扩展都不是活性所必需的。我们还发现，TnIYD可以有效地促进碘、溴和氯酪氨酸的脱卤，类似于人类和其他嗜中菌的脱碘酶。此外，2-碘酚是TnIYD的弱底物，就像迄今为止表征的所有其他iyd一样。与嗜热生物的酶一致，我们观察到与嗜热生物的酶相比，TnIYD具有致密的褶皱和低的表面积。从我们对TnIYD的调查中获得的见解表明，专注于与传统标准不同的序列，以揭示活动的最小要素，是有优势的。我们的结论是，tnyd现在代表了一个优越的起始结构，为未来的努力设计一个稳定的脱卤酶针对环境问题的卤酚。
The nitroreductase superfamily of enzymes encompasses many flavin mononucleotide (FMN)-dependent catalysts promoting a wide range of reactions. All share a common core consisting of an FMN-binding domain, and individual subgroups additionally contain one to three sequence extensions radiating from defined positions within this core to support their unique catalytic properties. To identify the minimum structure required for activity in the iodotyrosine deiodinase subgroup of this superfamily, attention was directed to a representative from the thermophilic organism Thermotoga neapolitana (TnIYD). This representative was selected based on its status as an outlier of the subgroup arising from its deficiency in certain standard motifs evident in all homologues from mesophiles. We found that TnIYD lacked a typical N-terminal sequence and one of its two characteristic sequence extensions, neither of which was found to be necessary for activity. We also show that TnIYD efficiently promotes dehalogenation of iodo-, bromo-, and chlorotyrosine, analogous to related deiodinases (IYDs) from humans and other mesophiles. In addition, 2-iodophenol is a weak substrate for TnIYD as it was for all other IYDs characterized to date. Consistent with enzymes from thermophilic organisms, we observed that TnIYD adopts a compact fold and low surface area compared with IYDs from mesophilic organisms. The insights gained from our investigations on TnIYD demonstrate the advantages of focusing on sequences that diverge from conventional standards to uncover the minimum essentials for activity. We conclude that TnIYD now represents a superior starting structure for future efforts to engineer a stable dehalogenase targeting halophenols of environmental concern.
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DOI：
10.1073/pnas.1706849114
发表时间：
2017-11-07
影响因子：
11.1
作者：
Akiva E;Copp JN;Tokuriki N;Babbitt PC
通讯作者：
Babbitt PC
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影响因子：
4.5
作者：
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通讯作者：
Horvitz HR
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
--
作者：
Koziol, J.
通讯作者：
Koziol, J.
影响因子：
2.9
作者：
Ingavat, Nattha;Kavran, Jennifer M.;Rokita, Steven E.
通讯作者：
Rokita, Steven E.