Janet Smith

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Margaret J. Hunter Collegiate Professor of Life Sciences and Professor of Biological Chemistry

Phone: 734.615.9564
Fax: 734.763.6492
JanetSmith@umich.edu

  • About

    Our research focuses on protein structure and function, using X-ray crystallography as a structural tool. The three major projects in the lab have as a theme the use of protein-protein interactions to regulate enzyme activity. First, the glutamine amidotransferases are a group of "complex" enzymes that catalyze multi-step reactions in multiple active sites. The amidotransferases produce the ammonia in one active site and channel it to a second active site in the same enzyme for additional reaction. An intricate set of conformational changes accomplishes the signaling and channeling necessary to achieve tightly coupled catalysis.

    The second research area is the replication complex of flaviviruses and alphaviruses, two families of human pathogens. These viruses have a plus-sense RNA genome that is translated by the host to produce a polyprotein consisting of enzymes for proteolytic processing, for replication of the viral genome, and for capping newly synthesized RNA. Several protein-protein and protein-RNA complexes regulate these fundamental catalytic activities are being identified and studied.

    The third project aims to understand how the multiple catalytic modules of polyketide synthases work together to produce specific antibiotic products. The catalytic modules of these enzymes are four- or five-domain proteins, each domain having a catalytic or carrier function.

    The three projects are excellent examples of how transient protein structures and conformational change are used to control enzyme activity. For the viral replicase and polyketide synthase projects, we employ new high-throughput methods to investigate which proteins, protein domains or protein complexes are most suited to structural study.

  • Education
    • Ph.D., University of Wisconsin-Madison
    • Postdoctoral Fellow, Naval Research Laboratory
  • Awards
    • Fellow of the American Association for the Advancement of Science
    • Herbert Newby McCoy Award - Purdue University, 2001
  • Research Areas of Interest
    • Research Focus: Protein Structure and Function using X-ray Crystallography
  • Selected Publications:
  • Articles