Dph3 Enables Aerobic Diphthamide Biosynthesis by Donating One Iron Atom to Transform a [3Fe-4S] to a [4Fe-4S] Cluster in Dph1-Dph2.
Dph3 Enables Aerobic Diphthamide Biosynthesis by Donating One Iron Atom to Transform a [3Fe-4S] to a [4Fe-4S] Cluster in Dph1-Dph2.
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DOI：
10.1021/jacs.1c03956
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发表时间：
2021-06-30
影响因子：
15
通讯作者：
Lin H
中科院分区：
文献类型：
--
作者：
Zhang Y;Su D;Dzikovski B;Majer SH;Coleman R;Chandrasekaran S;Fenwick MK;Crane BR;Lancaster KM;Freed JH;Lin H
所有自由基S-腺苷甲硫氨酸（自由基-SAM）酶，包括非经典自由基-SAM酶双苯二甲酰胺生物合成酶Dph 1-Dph 2，都需要至少一个[4Fe-4S]（Cys）3簇才能发挥活性。在自由基-SAM酶群落中众所周知，[4Fe-4S]（Cys）3簇是极其空气敏感的，并且需要严格的厌氧条件来体外重建活性。因此，在有氧生物体内，这些酶在氧气存在下如何发挥作用是一个有趣的问题。在酵母Dph 1-Dph 2中，我们发现与已知的氧敏感性一致，[4Fe-4S]簇很容易降解为[3Fe-4S]簇。值得注意的是，小的含铁蛋白Dph 3在自由基-SAM酶催化循环期间捐赠一个Fe原子以将Dph 1-Dph 2中的[3Fe-4S]簇转化为功能性[4Fe-4S]簇。这种在有氧环境中维持自由基-SAM酶活性的机制可能是普遍的，并且Dph 3样蛋白可能存在以保持其他自由基-SAM酶在有氧环境中的功能。
All radical S-adenosylmethionine (radical-SAM) enzymes, including the noncanonical radical-SAM enzyme diphthamide biosynthetic enzyme Dph1–Dph2, require at least one [4Fe–4S](Cys)3 cluster for activity. It is well-known in the radical-SAM enzyme community that the [4Fe–4S](Cys)3 cluster is extremely air-sensitive and requires strict anaerobic conditions to reconstitute activity in vitro. Thus, how such enzymes function in vivo in the presence of oxygen in aerobic organisms is an interesting question. Working on yeast Dph1–Dph2, we found that consistent with the known oxygen sensitivity, the [4Fe–4S] cluster is easily degraded into a [3Fe–4S] cluster. Remarkably, the small iron-containing protein Dph3 donates one Fe atom to convert the [3Fe–4S] cluster in Dph1–Dph2 to a functional [4Fe–4S] cluster during the radical-SAM enzyme catalytic cycle. This mechanism to maintain radical-SAM enzyme activity in aerobic environments is likely general, and Dph3-like proteins may exist to keep other radical-SAM enzymes functional in aerobic environments.
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影响因子：
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