Oxygen-17 NMR spectroscopy of biological systems

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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.