Spectroscopic studies of molybdenum enzymes

钼酶的光谱研究

• 批准号: 283315-2007
• 负责人: George, Graham
• 金额: $ 3.78万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2009
• 资助国家: 加拿大
• 起止时间: 2009-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=427186
• 关键词: Spectroscopic; studies; molybdenum; enzymes

Molybdenum is the only second-row transition element with a known function in animals. It fulfills functional roles in enzymes in almost all living creatures, from bacteria through plants to invertebrates and mammals. The molybdenum enzymes all contain the metal bound by an unusual sulfur-containing cofactor. Despite possessing common structural elements, the enzymes are remarkable in the range of different chemical reactions that are catalyzed, although almost all are two-electron oxidation-reduction reactions in which an oxygen atom is transferred to or from the molybdenum. The functional roles filled by molybdenum enzymes are equally diverse; for example, they play essential roles in microbial respiration, in the uptake of nitrogen in green plants, in controlling insect eye color, and in human health. The proposed work is a systematic study of all the major families of molybdenum enzymes using the synchrotron-based technique of X-ray absorption spectroscopy. We propose to use a novel holistic approach in combining information from X-ray absorption spectroscopy, advanced computer molecular modeling, and available protein crystal structures to obtain the most accurate picture yet of the active sites. The ultimate goal of the work is to develop an in-depth quantitative structural and electronic understanding of the catalytic mechanisms used by the enzymes, comparing and contrasting between and within the different families. This will lead to an improved understanding of how molybdenum enzymes achieve their remarkable functional diversity. The benefits of this research are three-fold. i) The results will yield detailed insights for an important group of enzymes. ii) The holistic approach developed will be broadly applicable to all metalloprotein studies. iii) The research will strengthen the Canadian effort in utilizing one of the major synchrotron tools in structural molecular biology - X-ray absorption spectroscopy.

钼是唯一的第二排过渡元素，在动物中具有已知的功能。它在几乎所有生物的酶中发挥功能作用，从细菌到植物，再到无脊椎动物和哺乳动物。所有的钼酶都含有由一种不寻常的含硫辅因子结合的金属。尽管具有共同的结构元素，酶在催化的不同化学反应的范围内是显着的，尽管几乎所有都是双电子氧化还原反应，其中氧原子转移到钼或从钼转移。钼酶的功能作用也同样多样，例如，它们在微生物呼吸、绿色植物的氮吸收、控制昆虫眼睛颜色和人类健康中发挥重要作用。拟议的工作是一个系统的研究所有主要家庭的钼酶使用同步加速器为基础的技术的X射线吸收光谱。我们建议使用一种新的整体方法，结合来自X射线吸收光谱，先进的计算机分子建模和可用的蛋白质晶体结构的信息，以获得最准确的活性位点的图片。这项工作的最终目标是对酶所使用的催化机制进行深入的定量结构和电子理解，比较和对比不同家族之间的差异。这将导致对钼酶如何实现其显着的功能多样性的更好的理解。这项研究的好处有三方面。i）结果将产生对一组重要酶的详细见解。ii）开发的整体方法将广泛适用于所有金属蛋白质的研究。㈢这项研究将加强加拿大在利用结构分子生物学的一个主要同步加速器工具-X射线吸收光谱学方面的努力。