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.

细菌中钼辅酶（MOCO）的生物合成涉及前体Z的初始形成，从5 GTP，其转化为钼翅目（MPT），将钼的插入MPT（MO-MPT）插入MPT（MO-MPT），以及通过二核代理的附件进一步修饰MP，（BIS-MGD）或大钼胞嘧啶二核苷酸辅因子（MCD）。通过在催化钼位中添加末端硫磺配体可以进一步修改MO-MPT或MCD。在合成moco-variants之后，必须将特定形式靶向相应的apo-酶。主要目标是分析MOCO插入到靶酶中的特异性，并指定蛋白质成分，例如Mocobinding Chaperones，参与此复制。此外，确定MO-MTP是否被修改为BIS-MGD或MCD的因素仅了解。 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.主要目标是了解细菌中MOCO的特定化合物的调节和相互作用。