Oxygen-17 NMR spectroscopy of biological systems

生物系统的氧 17 NMR 波谱

• 批准号: 203308-2011
• 负责人: Wu, Gang
• 金额: $ 6.19万
• 依托单位: Queen's University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=546318
• 关键词: Oxygen; 17; NMR; spectroscopy; biological

Nuclear magnetic resonance (NMR) spectroscopy is a powerful analytical technique for studying molecular structure, dynamics, and chemical bonding. The development of this technique over the past several decades has revolutionized chemical and biological sciences. However, most successful NMR applications to biological systems such as proteins and nucleic acids are primarily based on detection of atomic nuclei with a nuclear spin quantum number of 1/2 such as H-1, C-13, and N-15. On the other hand, the oxygen element, being one of the most abundant in organic and biological molecules, has not yet been readily accessible by NMR spectroscopy. This is mainly because the only NMR-active oxygen isotope, O-17, has a nuclear spin quantum number of 5/2, known as a quadrupolar nucleus. Unlike commonly used spin-1/2 nuclei, quadrupolar nuclei are notoriously difficult to study by NMR because they often give rise to very broad NMR signals. As a result, O-17 is very often considered to be "NMR invisible" especially in the context of biological macromolecules. Our recent work has solved this challenging problem. We have developed new NMR methods that allow detection of high resolution O-17 NMR spectra for biological macromolecules both in the solid state and in aqueous solution. This new O-17 NMR approach, being complementary to the existing H-1, C-13, and N-15 NMR methods, can yield unique information about molecular interactions. The primary objective of our proposed research program is to apply these new O-17 NMR methods to several important biological systems. In particular, we will study ligand binding to heme proteins and to detect enzymatic reaction intermediates related to serine protease catalysis. The ultimate goal of our research program is to make all major elements (H, C, N, and O) found in biological molecules equally accessible by NMR spectroscopy. We hope that by demonstrating the power of O-17 NMR in solving important biological problems, more researchers will consider to use this method for solving their own research problems. It is anticipated that, in the next 5 years, a total of 20 HQPs (4 PhD, 6 MSc, and 10 BSc students) will be trained in this research program.

核磁共振 (NMR) 光谱是一种用于研究分子结构、动力学和化学键合的强大分析技术。这项技术在过去几十年的发展彻底改变了化学和生物科学。然而，在蛋白质和核酸等生物系统中最成功的 NMR 应用主要基于对核自旋量子数为 1/2 的原子核（如 H-1、C-13 和 N-15）的检测。另一方面，氧元素是有机和生物分子中含量最丰富的元素之一，但尚未通过核磁共振波谱法轻易获得。这主要是因为唯一的核磁共振活性氧同位素O-17的核自旋量子数为5/2，被称为四极核。与常用的自旋 1/2 核不同，四极核很难通过 NMR 研究，因为它们经常产生非常宽的 NMR 信号。因此，O-17 通常被认为是“NMR 不可见的”，尤其是在生物大分子的背景下。我们最近的工作解决了这个具有挑战性的问题。我们开发了新的 NMR 方法，可以检测固态和水溶液中生物大分子的高分辨率 O-17 NMR 光谱。这种新的 O-17 NMR 方法是对现有 H-1、C-13 和 N-15 NMR 方法的补充，可以产生有关分子相互作用的独特信息。我们提出的研究计划的主要目标是将这些新的 O-17 NMR 方法应用于几个重要的生物系统。特别是，我们将研究配体与血红素蛋白的结合，并检测与丝氨酸蛋白酶催化相关的酶反应中间体。我们研究计划的最终目标是使生物分子中发现的所有主要元素（H、C、N 和 O）均可以通过 NMR 光谱法获取。我们希望通过展示O-17 NMR在解决重要生物学问题方面的力量，更多的研究人员会考虑使用这种方法来解决自己的研究问题。预计在未来5年内，该研究项目将培训总共20名HQP（4名博士生、6名硕士生和10名理学士生）。