FUNCTIONAL ANALOGUES OF HEMERYTHRIN

血红蛋白的功能类似物

• 批准号: 6183900
• 负责人: BRICE BOSNICH
• 金额: $ 20.32万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6183900
• 关键词: analog; chemical binding; chemical synthesis; hemerythrin; molecular site; protein structure function; synthetic protein

DESCRIPTION: (Applicant's abstract) Molecular oxygen is crucial for the survival of most forms of life. Living organisms absorb molecular oxygen by way of metal containing proteins. Higher organisms use iron coordinated to a heme (hemoglobin, myoglobin) to absorb and transport molecular oxygen. Other organisms use proximal copper ions to serve the same function. Biological studies on the proteins as well as chemical studies on analogues of the metal binding sites of these two classes of dioxygen carriers have provided a detailed understanding of how molecular oxygen is bound and released from the metals. The third major dioxygen transporting protein is hemerythrin which contains two non-heme iron atoms which serve to bind molecular oxygen. The molecular structures of a variety of hemerythrins have been known for some time and the dioxygen binding has been established but many important, subtle details of the process remain to be answered. As has been shown for the other proteins, one of the most effective ways of addressing these questions is to synthesize small analogues of the dioxygen binding site. So far no such analogues of hemerythrin have been prepared although excellent models which reproduce many of the physical properties of hemerythrin have been characterized. The mechanism by which hemerythrin binds dioxygen is extraordinarily subtle and has no synthetic precedent. Many poorly understood elements are present in the oxidation process. This proposal is directed at synthesizing analogues of the metal binding site of hemerythrin. These analogues incorporate many of the features found in the protein. The design is sufficiently flexible so as to allow for the identification of the factors which control molecular oxygen binding in the protein. The project will, therefore, provide detailed understanding of the mechanism at the molecular level. Such information is important not only in the short term understanding of the action of the protein but also has wide general implications in the harnessing of molecular oxygen as a fuel in the long term.

描述：（申请人的摘要）分子氧对于 大多数生命形式的生存。 生物体通过以下方式吸收分子氧 含有蛋白质的金属的方式。 高等生物利用铁来协调 血红素（血红蛋白、肌红蛋白）吸收和运输分子氧。 其他生物体使用近端铜离子来发挥相同的功能。 蛋白质的生物学研究以及类似物的化学研究 这两类双氧载体的金属结合位点有 提供了对分子氧如何结合的详细理解 从金属中释放出来。 第三种主要的双氧转运蛋白是 血红蛋白含有两个非血红素铁原子，用于结合 分子氧。 多种血红蛋白的分子结构 已经知道了一段时间并且双氧结合已经建立 但这一过程的许多重要、微妙的细节仍有待解答。 作为 已被证明对于其他蛋白质来说，这是最有效的方法之一 解决这些问题的方法是合成双氧的小类似物 结合位点。 迄今为止尚未制备出此类血红蛋白类似物 尽管优秀的模型再现了许多物理特性 血红蛋白已被表征。 血红蛋白的作用机制 与双氧的结合非常微妙，并且没有合成先例。 氧化过程中存在许多人们知之甚少的元素。 这 该提案旨在合成金属结合位点的类似物 血红蛋白。 这些类似物结合了许多在 蛋白质。 该设计足够灵活，可以 确定控制分子氧结合的因素 蛋白质。 因此，该项目将提供对 分子水平的机制。 这些信息不仅重要 对蛋白质作用的短期了解，但也有广泛的了解 利用分子氧作为燃料的一般意义 长期。