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。在过去的几十年中，这种技术的发展彻底改变了化学和生物科学。但是，大多数成功的NMR应用于蛋白质和核酸等生物系统，主要基于对原子核的检测，其核自旋量子数为1/2，例如H-1，C-13和N-15。另一方面，NMR光谱法尚未轻松访问有机和生物分子中最丰富的氧元素之一。这主要是因为唯一的NMR活性氧同位素O-17的核自旋量子数为5/2，称为四核核。与常用的自旋1/2核不同，NMR很难研究四核核，因为它们通常会产生非常宽的NMR信号。结果，通常认为O-17是“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，可以在固态和水溶液中检测到高分辨率O-17 NMR光谱用于生物学大分子。这种新的O-17 NMR方法是与现有的H-1，C-13和N-15 NMR方法互补的，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的是将这些新的O-17 NMR方法应用于几种重要的生物系统。特别是，我们将研究与血红素蛋白的配体结合，并检测与丝氨酸蛋白酶催化有关的酶促反应中间体。我们的研究计划的最终目标是使NMR光谱同样访问的生物分子中发现的所有主要元素（H，C，N和O）。我们希望通过证明O-17 NMR在解决重要生物学问题方面的力量，更多的研究人员将考虑使用此方法来解决自己的研究问题。可以预料，在未来5年中，将在该研究计划中对总共20个HQP（4博士学位，6个MSC和10名BSC学生）进行培训。