The importance of iron in the biosynthesis and assembly of [NiFe]-hydrogenases.
The importance of iron in the biosynthesis and assembly of [NiFe]-hydrogenases.
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DOI：
10.1515/bmc-2014-0001
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发表时间：
2014-03-01
影响因子：
--
通讯作者：
Sawers, R Gary
中科院分区：
文献类型：
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作者：
Pinske, Constanze;Sawers, R Gary
[NiFe]-氢化酶（Hyd）是催化分子氢可逆氧化成质子和电子的氧化还原活性金属酶。这些酶通常是异源二聚体，在其催化大亚基中具有独特的生物活性位点，并在小亚基中具有用于电子转移的铁硫（Fe-S）簇的互补。根据环境和代谢的要求，铁-硫簇继电器显示相当大的变化之间的氢，甚至采用高电位[4Fe-3S]簇改善耐氧性。一般的铁硫簇（Isc）机制是小亚基成熟所必需的，可能提供标准的[4Fe-4S]，然后根据需要原位修饰。活性位点中的[NiFe]辅因子也具有铁离子，其上连接有一个CO和两个CN-双原子配体。特定的辅助蛋白合成这些配体并将辅因子插入脱辅基氢化酶大亚基中。氨甲酰磷酸是CN-配体的前体，最近的实验证据表明，内源性产生的CO2可能是CO的前体之一。最近的进展还表明，负责辅因子生成的机器如何获得铁。铁进入细菌细胞的几个运输系统存在;然而，在大肠杆菌中，它主要是亚铁转运体FeO和铁-柠檬酸盐铁载体系统Fec参与运送金属用于Hyd生物合成。遗传分析提供了证据，在辅因子生物合成和酶组装，确保正确的时空成熟这些模块化的氧化还原酶的关键检查点的存在。
[NiFe]-hydrogenases (Hyd) are redox-active metalloenzymes that catalyze the reversible oxidation of molecular hydrogen to protons and electrons. These enzymes are frequently heterodimeric and have a unique bimetallic active site in their catalytic large subunit and possess a complement of iron sulfur (Fe-S) clusters for electron transfer in the small subunit. Depending on environmental and metabolic requirements, the Fe-S cluster relay shows considerable variation among the Hyd, even employing high potential [4Fe-3S] clusters for improved oxygen tolerance. The general iron sulfur cluster (Isc) machinery is required for small subunit maturation, possibly providing standard [4Fe-4S], which are then modified as required in situ. The [NiFe] cofactor in the active site also has an iron ion to which one CO and two CN- diatomic ligands are attached. Specific accessory proteins synthesize these ligands and insert the cofactor into the apo-hydrogenase large subunit. Carbamoyl phosphate is the precursor of the CN- ligands, and recent experimental evidence suggests that endogenously generated CO2 might be one precursor of CO. Recent advances also indicate how the machineries responsible for cofactor generation obtain iron. Several transport systems for iron into bacterial cells exist; however, in Escherichia coli, it is mainly the ferrous iron transporter Feo and the ferric-citrate siderphore system Fec that are involved in delivering the metal for Hyd biosynthesis. Genetic analyses have provided evidence for the existence of key checkpoints during cofactor biosynthesis and enzyme assembly that ensure correct spatiotemporal maturation of these modular oxidoreductases.