Epoxyqueuosine Reductase QueH in the Biosynthetic Pathway to tRNA Queuosine Is a Unique Metalloenzyme.
Epoxyqueuosine Reductase QueH in the Biosynthetic Pathway to tRNA Queuosine Is a Unique Metalloenzyme.
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DOI：
10.1021/acs.biochem.1c00164
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发表时间：
2021-10-26
期刊：
影响因子：
2.9
通讯作者：
Bruner SD
中科院分区：
文献类型：
--
作者：
Li Q;Zallot R;MacTavish BS;Montoya A;Payan DJ;Hu Y;Gerlt JA;Angerhofer A;de Crécy-Lagard V;Bruner SD
肌苷是一种结构独特、功能重要的tRNA修饰物，广泛存在于真核生物和细菌中。腺苷生物合成的最后一步是环氧腺苷的还原/脱氧以形成核碱基的环戊烯基序。化学是由结构和功能特征钴胺素依赖性QueG。然而，queG基因在几种细菌中不存在，否则保留了肌苷生物合成机制。IPR 003828家族（以前称为DUF 208）的成员最近被鉴定为QueG的非正性替代品，该家族被重命名为QueH。在这里，我们提出了结构表征的QueH从Thermotoga maritima。该结构揭示了一个不寻常的活性中心架构与[4Fe-4S]的光泽沿着与相邻的配位铁金属。辅因子和配位金属离子的并列预示了环氧肌苷的双电子还原/脱氧的独特机制。为了支持结构表征，提供了体外生物化学和基因组分析。总的来说，这项工作揭示了铁/硫依赖性酶化学的新多样性，以及对这种广泛保守的tRNA修饰的最后一步的新见解。
Queuosine is a structurally unique and functionally important tRNA modification, widely distributed in eukaryotes and bacteria. The final step of queuosine biosynthesis is the reduction/deoxygenation of epoxyqueuosine to form the cyclopentene motif of the nucleobase. The chemistry is performed by the structurally and functionally characterized cobalamin-dependent QueG. However, the queG gene is absent from several bacteria that otherwise retain queuosine biosynthesis machinery. Members of the IPR003828 family (previously known as DUF208) have been recently identified as non-orthologous replacements of QueG and this family was renamed QueH. Here we present the structural characterization of QueH from Thermotoga maritima. The structure reveals an unusual active site architecture with a [4Fe-4S] metallocluster along with an adjacent coordinated iron metal. The juxtaposition of cofactor and coordinated metal ion predicts a unique mechanism for a two electron reduction/deoxygenation of epoxyqueuosine. To support the structural characterization, in vitro biochemical and genomic analyses are presented. Overall, this work reveals new diversity in the chemistry of iron/sulfur dependent enzymes and novel insight into the last step of this widely conserved tRNA modification.
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影响因子：
5.7
作者：
Dutta, Anindita;Bahar, Ivet
通讯作者：
Bahar, Ivet
DOI：
10.1107/s0907444903018043
发表时间：
2003-11-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Grosse-Kunstleve, RW;Adams, PD
通讯作者：
Adams, PD
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：
13.8
作者：
Goodstadt, L;Ponting, CP
通讯作者：
Ponting, CP
影响因子：
15.9
作者：
de Crécy-Lagard V;Jaroch M
通讯作者：
Jaroch M