Smith unveils the secrets of nature’s catalysts

When Janet Smith was a student at Indiana University in Pennsylvania, she attended a seminar on the structure, sequence and phylogeny of cytochrome c. “I thought the protein was just wonderful,” she said. “I was fascinated by the structural details and how the conservation of cytochrome c sequences matched the 3D structure, but I didn’t have the opportunity to study protein structure until I was a postdoctoral fellow. It’s the discovery … Sometimes you look at a new protein structure and immediately say, “Oh, wow! Now I understand.’ It’s a great thrill.

Janet Smith

Some four decades later, Smith was still busy putting together structural protein puzzles when she learned that she had won the 2022 American Society’s Mildred Cohn Prize for Biochemistry and Molecular Biology in Biological Chemistry.

“It was a total surprise, a very pleasant surprise,” she said, describing the award as “recognition of my service activities to help advance the field of structural biology”.

In his laboratory at the University of Michigan, Smith and his team use x-ray crystallography, including the anomalous multi-wavelength diffraction method and its single-wavelength counterpart, known as MAD. and SAD, to resolve protein structures such as biosynthetic enzymes for natural products and primary metabolites. As a new assistant professor, her first research projects required specialized synchrotron beamlines, which led her to develop high performance beamlines for macromolecular crystallography.

“One of the most satisfying parts of my career has been watching my field move from ‘protein crystallography’ to ‘structural biology,’” Smith said. “I have been fortunate enough to see the structure of proteins become prospective in biochemistry and molecular biology, and no longer retrospective.”

Smith lectures internationally on structural biology and synchrotron radiation, and mentors young women scientists and young crystallographers, even if they are not working in his lab. Mentoring is her hardest job, she said. “Science is changing… and it can be difficult to choose a course of research. I advise new students to pick any area of ​​experience that they enjoy working in and think about areas that they think will be strong in 20 years. And then look at the intersection. And don’t be afraid to change course as science – and they – change. “

Decipher the structural puzzles

Janet Smith’s lab studies the biological function of proteins at the molecular level. They use X-ray crystallography to solve the 3D structures of proteins and then aim to explain what proteins do and how they do it.

“We try to explain the function of a protein in terms of the 3D structure, and then test ideas about the mechanism with biochemical and other experiments,” Smith said. She used this approach to understand the mechanism and regulation of several enzymes by solving their crystal structures.

In her awards talk, “Proteins in the Interaction of Viruses as Pathogens and Us as Hosts: ‘Us vs. Them’,” Smith will discuss her recent research, she said. His lab’s study of viral proteins revealed some unexpected mechanisms underlying host-virus interactions and the resulting immune response mechanisms.

“I’ll probably talk about one or two systems that we’ve studied,” she said, “and I’ll outline the structural features of the proteins humans make to fight RNA viruses.”

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