Probing the activities of the Ccm proteins of the cytochrome c biosynthesis system

蛋白质是复杂的生物分子，对所有活细胞的结构和功能至关重要。为了使其功能多样化，蛋白质使用称为辅因子的额外分子，其中有许多类型。血红素就是这样一种辅因子;它是一种中心有一个铁原子的有机化学物质，在不同的细胞过程中具有许多重要功能。许多含有血红素的蛋白质在细胞中形成后，会经历一个过程，在蛋白质和血红素之间形成键;这些被称为细胞色素c，在呼吸和涉及电子转移的反应中是必不可少的。事实上，细胞色素c被认为是进化中最早出现的蛋白质之一。在其他情况下，血红素与蛋白质结合而不与它们形成键，例如在血红蛋白中，血红蛋白使用血红素结合血液中的氧气。在血红素辅因子与细胞色素结合的情况下，需要其他蛋白质来帮助这种反应，这不是自发的。使用典型的实验室细菌E.大肠杆菌作为模型系统，我们研究了血红素的附着过程，这是一个复杂的过程，涉及大量的蛋白质。出乎意料的是，已经发现这些系统在不同类型的细胞中不同。我们提出的研究旨在使用各种实验方法和技术来了解这些蛋白质的功能。一旦我们阐明了血红素附着在细菌细胞色素上的细胞机制，我们就有可能设计出针对这些蛋白质的药物。这是可能的，因为人类存在一个完全不同的系统，将血红素附着在我们的细胞色素上，使我们能够选择性地靶向致病细菌。为了完整地描述构成生命的基本生化反应，理解细胞色素c的生成过程是一个基本的、中心的生物学过程也是很重要的。

Proteins are complex biomolecules that are essential to the structure and function of all living cells. In order to diversify their functions, proteins use additional molecules called cofactors, of which there are many types. Heme is one such cofactor; it is an organic chemical with an iron atom in the centre and has many essential functions in different cellular processes. Many proteins that contain heme undergo a process after they are made in the cell in which bonds are formed between the protein and the heme; these are called cytochromes c and are essential in respiration and in reactions that involve the transfer of electrons. In fact, cytochromes c are believed to be one of the earliest classes of protein to have appeared in evolution. In other cases, heme associates with proteins without forming bonds with them, for example in hemoglobin, which uses the heme to bind oxygen in blood. In the case where the heme cofactor becomes bonded to the cytochrome, other proteins are needed to assist in this reaction, which is not spontaneous. Using the prototypical laboratory bacterium E. coli as a model system, we study this process of heme attachment, which is complex and involves a large number of proteins. Unexpectedly, it has been found that these systems differ in different types of cells. Our proposed research seeks to understand how these proteins function, using a variety of experimental approaches and techniques. Once we have elucidated the cellular mechanisms of attaching heme to cytochromes in bacteria, we might have the possibility of designing drugs to target these proteins. This would be possible because a completely different system exists in humans to attach heme to our cytochromes, allowing us to selectively target disease-causing bacteria, for example. It is also important to understand the process of making cytochromes c as a fundamental and central biological process, in order to complete a description of the essential biochemical reactions that constitute life.