Double-cubane iron-sulfur clusters: a new cofactor in biology

双立方烷铁硫簇：生物学中的新辅助因子

• 批准号: 428096259
• 负责人: Professor Dr. Holger Dobbek
• 金额: --
• 依托单位: Arbeitsgruppe Strukturbiologie und Biochemie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/428096259?language=en
• 关键词: Double; cubane; iron; sulfur; clusters

Anaerobic bacteria employ complex metalloenzymes based on iron-sulfur clusters to convert gaseous substrates. Several of the catalyzed reactions are reductions attractive for energy conversion and conservation, among them the reduction of protons to dihydrogen and of carbon dioxide to carbon monoxide. When the reducing power of physiological electrons are not enough the achieve these conversions, electron may be energized beyond the physiological window by coupling ATP-hydrolysis to electron transfer against a redox potential gradient. The electron-accepting proteins typically contain unusual iron-sulfur clusters at which the catalytic reactions occur.Within this project I want to investigate the occurrence and function of a novel cofactor associated with ATP-driven electron transfer. The cofactor is formed by bridging two [Fe4S4]-clusters by a sulfide-ligand, forming an [Fe8S9]-cluster. This [Fe8S9]-cluster has been detected by us in an enzyme capable of reducing acetylene and hydrazine. However, based on sequence comparison and a conserved cluster-binding motif, we speculate that the [Fe8S9]-cluster is wide-spread in nature and occurs in at least three different classes of enzymes. Within this project, I want (I) to produce and study members of all three classes potentially containing the [Fe8S9]-cluster, to see if there are indeed three enzymes classes of distinct structure carrying the novel cofactor. (II) I want to reveal the potential physiological role(s) of the cofactor by studying its reactivity and the substrate binding selectivity of the associated protein matrizes. Characterizing a novel iron-sulfur cluster and novel enzymes, requires input from different expertise ranging from physiological assays to the biophysical characterization of iron-sulfur proteins and is therefore attempted within the priority program "Iron-Sulfur for Life". In a side project, I want to continue a joint approach within the same priority program in which we combine vibrational spectroscopy and X-ray crystallography at single crystals to gain further insights into the mechanism of reversible hydrogen cycling of a [NiFe]-containing hydrogenase.

厌氧细菌利用基于铁硫簇的复合金属酶来转化气态底物。有几种催化反应是对能量转换和保存有吸引力的还原反应，其中包括质子还原为二氢和二氧化碳还原为一氧化碳。当生理电子的还原能力不足以实现这些转换时，可以通过将ATP水解耦合到电子转移以对抗氧化还原电位梯度而使电子在生理窗口之外通电。电子接受蛋白质通常含有不寻常的铁硫簇，在催化反应发生。在这个项目中，我想调查的发生和功能的一种新的辅因子与ATP驱动的电子转移。辅因子是通过硫化物配体桥接两个[Fe 4S 4]-簇形成的，形成[Fe 8 S9]-簇。我们在一种能够还原乙炔和肼的酶中检测到这种[Fe 8 S9]簇。然而，基于序列比较和保守的簇结合基序，我们推测[Fe 8 S9]-簇在自然界中是广泛分布的，并且发生在至少三种不同类别的酶中。在这个项目中，我想（I）生产和研究可能含有[Fe 8 S9]-簇的所有三类酶的成员，看看是否确实有三种不同结构的酶携带新的辅因子。(II)我想通过研究其反应性和相关蛋白基质的底物结合选择性来揭示辅因子的潜在生理作用。表征一种新的铁硫簇和新的酶，需要从不同的专业知识，从生理测定铁硫蛋白的生物物理特性的输入，因此试图在优先计划“铁硫生命”。在一个附带项目中，我想继续在同一优先项目中的联合方法，其中我们将联合收割机振动光谱和X射线晶体学结合在单晶中，以进一步了解含[NiFe]氢化酶的可逆氢循环机制。