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The modification and targeting of complex metal-cofactors into their apo-enzymes

将复杂的金属辅因子修饰并靶向其脱辅基酶

基本信息

批准号：
157108951
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：
Research Grants
财政年份：
2009
资助国家：
德国
起止时间：
2008-12-31 至 2017-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/157108951?language=en
关键词：
modification targeting complex metal cofactors

项目摘要

The biosynthesis of the molybdenum cofactor (Moco) in bacteria involves the initial formation of Precursor Z from 5 GTP, its conversion to molybdopterin (MPT), insertion of molybdenum into MPT (Mo-MPT), and further modification of Mo-MPT by the attachment of different nucleofides either forming the bis-molybdopterin dinucleotide cofactor (bis-MGD) or the molybdopterin cytosine dinucleotide cofactor (MCD). Mo-MPT or MCD can be further modified by the addition of a terminal sulfido ligand to the catalytic molybdenum site. After the synthesis of the Moco-variants, the specific form has to be targeted to the respective apo-enzyme. The main goal is to analyze the specificity of Moco insertion into target enzymes and to specify the protein components, e.g. Mocobinding chaperones, involved in this reacfion. In addition, the factors that determine whether Mo- MPT is modified to bis-MGD or MCD are only poorly understood. We will use two different model systems to study the modificafion and targeting of Moco in the cell: the well defined Escherichia coli system, containing enzymes that either bind Mo-MPT, bis-MGD or sulfurated MCD, and the simpler Rhodobacter capsulatus system, which contains only two forms of Moco: sulfurated Mo- MPT and bis-MGD. The main goal is to understand the regulafion and interplay of the specific compounds involved in the maturafion and specific distribution of Moco in bacteria.

钼辅因子（Moco）在细菌中的生物合成涉及从5-GTP初始形成前体Z，其转化为多蝶呤（MPT），钼插入MPT（Mo-MPT），以及通过连接不同的核苷酸进一步修饰Mo-MPT，形成双-多蝶呤二核苷酸辅因子（bis-MGD）或多蝶呤胞嘧啶二核苷酸辅因子（MCD）。Mo-MPT或MCD可以通过向催化钼位点添加末端硫基配体来进一步修饰。在Moco变体合成后，必须将特定形式靶向相应的脱辅基酶。主要目标是分析Moco插入靶酶的特异性，并指定参与该反应的蛋白质组分，例如Mocobinding分子伴侣。此外，决定Mo-MPT是否被修饰为双-MGD或MCD的因素仅知之甚少。我们将使用两种不同的模型系统来研究Moco在细胞中的修饰和靶向：明确定义的大肠杆菌系统，其含有结合Mo-MPT、双-MGD或硫化MCD的酶，以及更简单的荚膜红杆菌系统，其仅含有两种形式的Moco：硫化Mo-MPT和双-MGD。主要目的是了解参与Moco在细菌中成熟和特异性分布的特定化合物的调节和相互作用。