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The deep structural understanding of the ribosome offered by Tom Steitz's team is enabling Rib-X, the company he cofounded, to invent new antibiotics.
As Perutz stood under the molecule pointing out features now familiar to any freshman biochemistry student, Steitz remembers thinking, “‘Wow. This is the way to understand biological molecules.’ And I wanted to do it.”
So he did. And 47 years later, Steitz, an HHMI investigator since 1986, joined Venkatraman Ramakrishnan of the MRC Laboratory of Molecular Biology in England and Ada Yonath of the Weizmann Institute of Science in Israel in winning the 2009 Nobel Prize in Chemistry.
The trio, working independently, used the same basic techniques as Perutz to scale the Mount Everest of biological molecules—the ribosome. Weighing in at more than 150,000 atoms, the ribosome is the engine of life, a delightfully intricate cellular gizmo that churns out countless billions of proteins that brick by biological brick build bacteria, birds, and biochemists. As Steitz's map of the large subunit of the ribosome helped show, the structure reaches back to the very beginning of cellular life on Earth, some two billion years ago.
Decoding its structure afforded a glimpse into that almost unknowable past—and offered a roadmap to the future of antibiotics. “I've hiked up a lot of mountains,” says Steitz, speaking literally and metaphorically, “and when we got that first glimpse of the ribosome, well, that was the view from the top.”
It's Thanksgiving week; the Yale University campus is half empty. But Steitz's lab hums with a dozen workers mapping the molecules of life. Steitz arrives at 10:30 a.m., fresh from the gym and relaxed in a fleece pullover—a hale, white-topped, and bearded 69-year-old still feeling a “subdued glow,” as his wife Joan puts it, from the Nobel announcement six weeks prior.
As Steitz chats, laughing easily, he remembers things to do— come up with a title for his upcoming Nobel speech, send an artifact to the Nobel museum, revisit a manuscript with a postdoc. He grabs a colorful plastic model of a ribosome—a grapefruit-sized riot of blue, red, yellow, green, and purple whorls—and mutters, “Maybe I'll send them this.”
Steitz returns the model to a low cabinet packed with a dozen more, all molecules he has mapped over four decades.
Photo: Paul Fetters