Janet L. Smith

Biosketch

Janet Smith is a structural biologist recognized for her work on protein structure and function and for her advancement of the uses of synchrotron radiation in structural biology. She is known particularly for her studies on enzymes with multiple active sites, including natural product biosynthetic enzymes and glutamine amidotransferases, and for her studies of host and virulence factors that affect viral pathogenesis. Smith was born and grew up in the suburbs of Philadelphia. She graduated from Indiana University of Pennsylvania, Indiana, Pennsylvania with a B.S. degree in chemistry and from the University of Wisconsin?Madison in 1978 with a Ph.D. in biochemistry. She was a National Research Council postdoctoral fellow in protein crystallography with Wayne Hendrickson at the Naval Research Laboratory in Washington, DC and Associate Research Scientist at Columbia University and the Howard Hughes Medical Institute. She joined the faculty of Purdue University in 1987 and relocated to the University of Michigan in 2005. She is a Fellow of the American Association for the Advancement of Science and the American Crystallographic Association and a member of the National Academy of Sciences.

Research Interests

Janet Smith's laboratory studies protein structure and function. They contributed to understanding how enzymes coordinate the activities of multiple active sites in their discovery that distinct active sites catalyze the two half-reactions in all glutamine amidotransferase families. Their studies of natural product biosynthetic enzymes have provided structure-based explanations of substrate and product selectivity. They discovered how nature adapted a number of common enzyme types for catalysis of rare and unexpected reactions. Their studies of viral and host proteins have led to structure-based explanations for aspects of the pathogenesis of flaviviruses and retroviruses. The NS1 virulence factor is a molecular jack-of-all-trades in which distinct domains of the flavivirus protein contribute to essential functions in viral replication, in immune evasion and in enhancing viral entry. Structural studies from the Smith lab demonstrated how the human APOBEC3H restriction factor recognizes a folded region in the 5' leader of the HIV-1 genome. The virus responds with a factor that targets the restriction factor for degradation. In another study, they demonstrated how the human zinc-finger antiviral protein recognizes CpG dinucleotides in viral RNAs, explaining the depletion of CpG in coding regions of the viral genome.