DNP SSNMR Spectrometer for Biomolecular Studies We propose the purchase of a Dynamic Nuclear Polarization (DNP) Solid State NMR (SSNMR) spectrometer at 600 MHz. Over the past decade Magic Angle Spinning based Solid State NMR (MAS SSNMR) has made rapid progress, including spectral assignments of many different kinds of proteins, determination of atomic-resolution structures, and applications to disease related proteins that are inaccessible by other methods. Broader biomedical impact of these methods is clearly hampered by the notoriously poor detection sensitivity of SSNMR. DNP is a recently established method to improve detection sensitivity by an astonishing one to two orders of magnitude, via irradiation of exogenous stable free radicals. We present initial spectra, captured in only a few hours on this new-generation instrument at the manufacturer's (Bruker BioSpin) demonstration site, with no previous experience with the spectrometer. The spectra are very encouraging, validating that the instrumentation operates stably enough for multidimensional spectroscopy. Moreover, several samples, representative of the proposed research topics, exhibit strong enhancements, and give high quality spectra. Several NIH-funded investigators will gather detailed, otherwise unavailable, structural information on proteins that play key roles in: neurodegeneration and aging (Alzheimer's A2, synuclein, tau, human prion protein, actin), cardiovascular disease (potassium channels and homologs), pulmonary disease (beta-2-adrenergic receptor) and infectious diseases (HIV capsid, multiple drug resistance factor from S. aureus, ATP synthase from M. tuberculosis). ESR and NMR experts will collaborate to ensure effective and innovative use of the instrument. Staff devoted to the proposed instrument will help disseminate instruction on the methods, to facilitate collaboration among biochemistry laboratories in the 10 member institution of the New York Structural Biology Consortium. )

Public Health Relevance

We propose the purchase of a new-generation Dynamic Nuclear Polarization Solid State NMR spectrometer at 600 MHz, which will provide detailed, otherwise unavailable, structural information on proteins that play key roles in neurodegeneration and aging, cardiovascular disease, pulmonary disease and infectious diseases. On funding, the purchase would protect American jobs, both in the American corporate supplier (Bruker BioSpin in Billerica, MA) and in the host laboratory, a consortium of 10 member institutions of the New York Structural Biology Consortium.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biomedical Research Support Shared Instrumentation Grants (S10)
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Special Emphasis Panel (ZRG1-BCMB-N (30))
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Levy, Abraham
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New York Structural Biology Center
New York
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Rogawski, Rivkah; Sergeyev, Ivan V; Li, Yongjun et al. (2017) Dynamic Nuclear Polarization Signal Enhancement with High-Affinity Biradical Tags. J Phys Chem B 121:1169-1175
Sergeyev, Ivan V; Itin, Boris; Rogawski, Rivkah et al. (2017) Efficient assignment and NMR analysis of an intact virus using sequential side-chain correlations and DNP sensitization. Proc Natl Acad Sci U S A 114:5171-5176
Xu, Yimin; Lorieau, Justin; McDermott, Ann E (2010) Triosephosphate isomerase: 15N and 13C chemical shift assignments and conformational change upon ligand binding by magic-angle spinning solid-state NMR spectroscopy. J Mol Biol 397:233-48