Coordination Funds

协调基金

• 批准号: 310614238
• 负责人: Professorin Dr. Silke Leimkühler
• 金额: --
• 依托单位: Arbeitsgruppe für Molekulare Enzymologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/310614238?language=en
• 关键词: Coordination; Funds

Iron-sulfur (FeS) centers are essential protein cofactors in all forms of life. They are involved in many of the key biological processes including respiration, photosynthesis, metabolism of nitrogen, sulfur, carbon and hydrogen, biosynthesis of antibiotics, gene regulation, protein translation, replication and DNA repair, protection from oxidizing agents, and neurotransmission. In particular, FeS centers are not only involved as enzyme cofactors in catalysis and electron transfer, but they are also indispensable for the biosynthesis of complex metal-containing cofactors. A prominent example is represented by the family of radical/S-adenosylmethionine-dependent enzymes, which were discovered in 2001. Members of this family play essential roles in the biosynthesis of metal centers as complex as the iron-molybdenum cofactor (FeMoco) of nitrogenase, the molybdenum cofactor (Moco) of various molybdoenzymes, the active sites of [Fe-Fe]- and [Fe]-hydrogenases and the tetrapyrrole cofactors of hemes, corrins and chlorins. In spite of the recent fundamental breakthroughs in metalloenzyme research, it has become evident that studies on single enzymes have to be transformed into the broader context of a living cell where biosynthesis, function, and disassembly of these fascinating metal cofactors are coupled in a dynamic fashion. The various biosynthetic pathways were found to be tightly interconnected through a complex crosstalk mechanism that involves the dependence on the bio-availability of distinct metal ions, in particular molybdenum, iron, tungsten and nickel. The current lack of knowledge of such interaction networks is due to the sheer complexity of the metal cofactor biosynthesis with regard to both the (genetic) regulation and (chemical) metal center assembly. Recent pioneering technical developments allowed the detailed investigation of the assembly, biosynthesis and catalysis of FeS-dependent enzymes in a cellular context, opening up a new era in studying metalloenzymes. Such studies are not only important for understanding fundamental cellular processes but they are also a prerequisite for providing a comprehensive view of the complex biosynthesis and the catalytic mechanism of metalloenzymes that underlie metal-related human diseases. These key features of metalloenzymes can only be implemented in a cellular context. Understanding the crosstalk of metal ions on a cellular basis requires multidisciplinary cooperative approaches that span the entire range from molecular biology, inorganic chemistry, biochemistry, cell biology, and structural biology to theory and spectroscopy. In the SPP it is planned to study novel enzyme mechanisms, innovative model complexes, and new biogenesis pathways in the physiological context of metalloenzymes in living organisms.

铁硫（FeS）中心是所有生命形式中必不可少的蛋白质辅因子。它们参与许多关键的生物过程，包括呼吸，光合作用，氮，硫，碳和氢的代谢，抗生素的生物合成，基因调控，蛋白质翻译，复制和DNA修复，保护免受氧化剂和神经传递。特别是，FeS中心不仅作为酶辅因子参与催化和电子传递，而且它们对于复杂的含金属辅因子的生物合成也是不可或缺的。一个突出的例子是2001年发现的自由基/S-腺苷甲硫氨酸依赖性酶家族。该家族的成员在金属中心的生物合成中起重要作用，如固氮酶的铁-钼辅因子（FeMoco）、各种脱氢酶的钼辅因子（Moco）、[Fe-Fe]-和[Fe]-氢化酶的活性位点以及血红素、咕啉和二氢卟啉的四吡咯辅因子。尽管最近在金属酶的研究取得了根本性的突破，但很明显，对单一酶的研究必须转化为活细胞的更广泛背景，在活细胞中，这些迷人的金属辅因子的生物合成，功能和分解以动态的方式耦合。发现各种生物合成途径通过复杂的串扰机制紧密互连，该串扰机制涉及对不同金属离子（特别是钼、铁、钨和镍）的生物可用性的依赖。目前缺乏这种相互作用网络的知识是由于金属辅因子生物合成的（遗传）调节和（化学）金属中心组装的绝对复杂性。最近的开创性技术发展允许在细胞环境中详细研究FeS依赖性酶的组装，生物合成和催化，开辟了研究金属酶的新时代。这些研究不仅对理解基本的细胞过程很重要，而且也是提供复杂的生物合成和金属酶催化机制的综合观点的先决条件，金属酶是金属相关人类疾病的基础。金属酶的这些关键特征只能在细胞环境中实现。理解细胞基础上的金属离子的串扰需要多学科的合作方法，跨越从分子生物学，无机化学，生物化学，细胞生物学和结构生物学的理论和光谱学的整个范围。在SPP中，计划研究新的酶机制，创新的模型复合物和新的生物合成途径，在生物体中金属酶的生理背景下。