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NIDDK Installs New Spectrometer

By Sharon Ricks

"It wasn't your typical office move," says Dr. Angela Gronenborn, about the 10-foot-tall 3,527-pound 750 megaHertz nuclear magnetic resonance (NMR) spectrometer recently installed in Bldg. 5.

To lower the giant magnet into the subbasement, more than a foot of brick was removed from the top of the rear entrance, ceiling beams were dislodged, and the freight elevator was pulled out of the way. "It wasn't easy, but everything went smoothly," says Gronenborn, who is chief of the structural biology section in NIDDK's Laboratory of Chemical Physics.

The biggest and most powerful spectrometer at NIH was purchased by NIDDK's LCP, NIDR, and the Intramural AIDS Targeted Antiviral Program. It has the capacity to analyze the structure of AIDS proteins, reveal the three-dimensional structures of large cancer molecules and ultimately open new avenues of research at NIDDK.

"It brings our equipment up to speed with that of the other major NMR laboratories, including one at the Department of Energy," Gronenborn says. The magnet will be used by four NIDDK research groups, headed by Drs. Adriaan Bax, Marius Clore, Gronenborn, and Robert Tycko, and one NIDR research group led by Dr. Dennis Torchia.

The NIDDK lab, in collaboration with others in NIAMS, recently found an unexpected fold in the solution structure of HIV-1 Nef using a 600 MHz spectrometer. The fold suggests a target for anti-HIV drug design. "Our findings are promising," says Gronenborn. "But the 750 MHz would have eliminated problems we experienced with aggregation and allowed us to work with protein solutions at reduced concentrations."

The larger magnet also has a higher spectral resolution to analyze larger and more complicated proteins such as HIV-1 protease-drug complexes. It provides more detailed pictures of the dynamics of proteins and protein-ligand complexes, helping researchers understand how large, complex molecules cause disease and identify options for preventing or altering the disease process.

NIDDK's first NMR spectrometer, purchased in the summer of 1957, was 40 MHz. "It was marvelous to have an NMR spectrometer at that time," says Dr. Edwin Becker, chief of the NMR section. "Organic chemists came to see whether that big machine would tell them what compound they had isolated or synthesized, and often it did!" Since then the field of NMR has increased dramatically. NIDDK graduated to the 60 MHz, then the 220, and then the 270, which was the only superconducting NMR system in the southeastern part of the country for almost a decade, says Becker. Today, NIH researchers hope the 750's ability to image complex molecules will boost chemical and biochemical research both in and outside of NIH.

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