Residue Mutations in [Fe-Fe]-hydrogenase Impedes O(2) Binding: A QM/MM Investigation.
Residue Mutations in [Fe-Fe]-hydrogenase Impedes O(2) Binding: A QM/MM Investigation.
复制标题
[Fe-Fe]-氢化酶中的残基突变阻碍 O(2) 结合：QM/MM 调查。
DOI：
10.1002/qua.22331
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发表时间：
2009
影响因子：
2.2
通讯作者：
Gogonea,Valentin
中科院分区：
文献类型：
--
作者：
Dogaru,Daniela;Motiu,Stefan;Gogonea,Valentin
[FeOFe]-氢化酶是可逆地催化质子和电子到分子氢的反应的酶，其发生在厌氧介质中。在生命系统中，[FeOFe]-氢化酶主要用于产生H2。[FeOFe]-氢化酶H-簇是活性位点，其含有两个铁原子。最新的理论研究（Tye等人，Inorg Chem，2008，47，2380; Liu和Hu，J Am Chem Soc，2002，124，5175）主张二铁空气抑制物质的结构是Fep IIOF化的11000 H或Fep IIOF化的110000 H，因此必须防止O2在所有二铁子簇氧化态下与Fed结合以保留催化活性酶。通过对[FeOFe]-氢化酶进行残基突变1，我们能够削弱O2与脱硫脱硫弧菌氢化酶（DdH）远端铁（Fed）的结合。个别残基删除进行了8个apapoenzyme层从美联储径向向外，以确定应进行哪些残基取代，以削弱O2结合。残基缺失和取代进行了三个二铁亚群氧化态，Fep IIOFed II，Fep IIOFed I，和Fep IOFed I的[FeOFe]-氢化酶。两个缺失（Thr 152和Ser 202）被认为是最有效的削弱O2结合到美联储在Fep IIOFed I氢化酶（GQM/MM 5.4千卡/摩尔）。还发现Fep IIOFed II和Fep IOFed I氢化酶的吉布斯能分别增加（2.2和4.4 kcal/mol）。-回复：V. Gogonea;电子邮件：v. gogonea@ csuohio。合同资助赞助商：能源部。合同授权编号：DE-FG 02 - 03 ER 15462。合同资助赞助商：美国国立卫生研究院。合同授予编号：1 R15 GM 070469 -01。其他支持信息可以在本文的在线版本中找到。1采用QM/MM [DFT/UFF]混合方法（Gaussian 03）。
[FeOFe]-hydrogenases are enzymes that reversibly catalyze the reaction of protons and electrons to molecular hydrogen, which occurs in anaerobic media. In living systems,[FeOFe]-hydrogenases are mostly used for H2 production. The [FeOFe]-hydrogenase H-cluster is the active site, which contains two iron atoms. The latest theoretical investigations (Tye et al., Inorg Chem, 2008, 47, 2380; Liu and Hu, J Am Chem Soc, 2002, 124, 5175) advocate that the structure of di-iron air inhibited species are either Fep IIOFed IIOOOH, or Fep IIOFed IIOOOOOH, thus O2 has to be prevented from binding to Fed in all di-iron subcluster oxidation states in order to retain a catalytically active enzyme. By performing residue mutations1 on [FeOFe]-hydrogenases, we were able to weaken O2 binding to distal iron (Fed) of Desulfovibrio desulfuricans hydrogenase (DdH). Individual residue deletions were carried out in the 8 Å apoenzyme layer radially outward from Fed to determine what residue substitutions should be made to weaken O2 binding. Residue deletions and substitutions were performed for three di-iron subcluster oxidation states, Fep IIOFed II, Fep IIOFed I, and Fep IOFed I of [FeOFe]-hydrogenase. Two deletions (Thr152 and Ser202) were found most effective in weakening O2 binding to Fed in Fep IIOFed I hydrogenase (GQM/MM 5.4 kcal/mol). An increase in Gibbs energy (2.2 and 4.4 kcal/mol) has also been found for Fep IIOFed II and Fep IOFed I hydrogenase, respectively.-backdonationCorrespondence to: V. Gogonea; e-mail: v. gogonea@ csuohio. edu Contract grant sponsor: Department of Energy. Contract grant number: DE-FG02-03ER15462. Contract grant sponsor: National Institutes of Health. Contract grant number: 1R15GM070469-01. Additional Supporting Information may be found in the online version of this article. 1In this investigation, QM/MM [DFT/UFF] hybrid method (Gaussian03) has been used.