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）中心是各种生命形式中必不可少的蛋白质辅因子。他们参与了许多关键的生物学过程，包括呼吸，光合作用，氮的代谢，硫，碳和氢的代谢，抗生素的生物合成，基因调节，蛋白质翻译，复制和DNA修复，保护剂，免受氧化剂的保护以及神经转移。特别是，FES中心不仅作为酶辅因子参与催化和电子转移，而且对于含有复杂金属辅助因子的生物合成也是必不可少的。一个突出的例子是由2001年发现的激进/s-腺苷甲硫代依赖性酶的家族表示。该家族的成员在金属中心的生物合成中起着重要作用，如硝基化合物（femococo），硝基基因酶（femococo），硝基激素酶，莫尔顿cofactor（Molybenum cofactor of Cofactor of Cofactor of Cofactor of Cofactor sosemy of Cofactor of Mooco）各种各样的MOOCOCO群体， [Fe-Fe] - 和[Fe] - 氢化酶以及Hemes，Corrins和Corrins和氯蛋白的四吡咯的辅助因子。尽管最近在金属酶研究中取得了最新的突破，但很明显，必须将对单个酶的研究转化为生物合成，功能和这些迷人金属辅助因子的生物合成，功能和拆卸的更广泛的背景，以动态方式耦合。发现各种生物合成途径通过复杂的串扰机制紧密互连，该机制涉及对不同金属离子的生物可用性，特别是钼，铁，钨和镍的依赖。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在（遗传）调节和（化学）金属中心组装方面的纯粹复杂性。最近的开创性技术发展允许对细胞环境中FES依赖性酶的组成和催化的详细研究，在研究冶金酶时开辟了一个新时代。此类研究不仅对于理解基本细胞过程很重要，而且它们也是对复杂的生物合成的全面观察的先决条件，以及与金属相关的人类疾病构成的金属酶的催化机制。金属酶的这些关键特征只能在细胞环境中实现。在细胞基础上了解金属离子的串扰需要多学科的合作方法，这些方法涵盖了从分子生物学，无机化学，生物化学，细胞生物学和结构生物学到理论和光谱学的整个范围。在SPP中，计划研究新颖的酶机制，创新模型复合物和新生物发生途径在生物中金属酶的生理环境中。