Graduate students in biochemistry and chemical biology meld molecular and structural biology with physical, organic and analytical chemistry to understand the molecular basis of biological processes and of human disease. Research in the Biochemistry and Chemical Biology Division focuses on the structure and function of proteins, membranes, DNA, RNA, large macromolecular complexes and viruses, natural product biogenesis, synthetic biology, and genomics.
Students are a constant source of new hypotheses for mechanisms underlying cellular machines like the ribosome and spliceosome, and for the protein and RNA folding problems. Students tackle these problems using biochemical methods, chemical biosensor technologies, protein and nucleic acid crystallography, in vitro and in vivo evolution, multi-dimensional NMR spectroscopy, surface chemistry, atomic force microscopy, fluorescence spectroscopy, and high-resolution mass spectrometry.
Doctoral students in Biochemistry and Chemical Biology leave the Department broadly trained for leadership roles in academia and industry.
As described in Angewandte Chemie, lipidated light-responsive constructs that sequester bioagents to the membranes of organelles and cells have been constructed in a collaboration between the Allbritton and Lawrence groups.
When membrane-bound, the bioagent is not susceptible to processing by its biological target. Photolysis releases the bioagent from its membrane anchor and thereby renders it biologically active.
Whole-cell catalysts for non-natural chemical reactions will open new routes to sustainable production of chemicals. Researchers in the Brustad Group have designed a cytochrome 'P411' with unique serine-heme ligation that catalyzes efficient and selective olefin cyclopropanation in intact Escherichia coli cells. Their findings have been published in Nature Chemical Biology.
The mutation C400S in cytochrome P450BM3 gives a signature ferrous CO Soret peak at 411 nm, abolishes monooxygenation activity, raises the resting-state FeIII-to-FeII reduction potential and substantially improves NAD(P)H-driven activity.
This paper has been selected and featured as an Editor's Choice in the latest issue of Science.
The Cellular Environment Stabilizes Adenine Riboswitch RNA Structure. Jillian Tyrrell, Jennifer L. McGinnis, Kevin M. Weeks, and Gary J. Pielak . Biochemistry, Article ASAP, DOI: 10.1021/bi401207q.
Impact of Reconstituted Cytosol on Protein Stability. Mohona Sarkar, Austin E. Smith, and Gary J. Pielak. Published online before print, November 11, 2013, doi: 10.1073/pnas.1312678110 PNAS November 11, 2013.
Molecular Basis for pH-Dependent Mucosal Dehydration in Cystic Fibrosis Airways. Alaina L. Garlanda, William G. Waltonb, Raymond D. Coakley, Chong D. Tan, Rodney C. Gilmore, Carey A. Hobbs, Ashutosh Tripathy, Lucy A. Clunes, Sompop Bencharit, M. Jackson Stutts, Laurie Betts, Matthew R. Redinbo, and Robert Tarran. PNAS, September 16, 2013, doi: 10.1073/pnas.1311999110.
β-Turn Sequences Promote Stability of Peptide Substrates for Kinases Within the Cytosolic Environment. Shan Yang, Angela Proctor, Lauren L. Cline, Kaiulani M. Houston, Marcey L. Waters and Nancy L. Allbritton. Analyst, 2013,138, 4305-4311.
Lipid Pools As Photolabile "Protecting Groups": Design of Light-Activatable Bioagents. Luong T. Nguyen, Nathan P. Oien, Nancy L. Allbritton, David S. Lawrence. Angew. Chem., online 31 JUL 2013, DOI: 10.1002/anie.201305510.
A Serine-Substituted P450 Catalyzes Highly Efficient Carbene Transfer to Olefins In Vivo. Pedro Coelho, Jane Wang, Maraia Ener, Stefanie Baril, Arvind Kannan, Frances Arnold, and Eric Brustad. Nature Chemical Biology (2013) doi:10.1038/nchembio.1278.
Accurate SHAPE-Directed RNA Secondary Structure Modeling, Including Pseudoknots. Christine E. Hajdin, Stanislav Bellaousov, Wayne Huggins, Christopher W. Leonard, David H. Mathews, and Kevin M. Weeks. PNAS, 110 (14):5498-5503.
A Synthetic Receptor for Asymmetric Dimethyl Arginine. Lindsey I. James , Joshua E. Beaver , Natalie W. Rice , and Marcey L. Waters. J. Am. Chem. Soc., 2013, 135 (17), pp 6450–6455.
Long-Range Architecture in a Viral RNA Genome. Eva J. Archer, Mark A. Simpson, Nicholas J. Watts, Rory O'Kane, Bangchen Wang, Dorothy A. Erie, Alex McPherson, and Kevin M. Weeks. Biochemistry, 2013, 52 (18), pp 3182–3190.
A Guanosine-Centric Mechanism for RNA Chaperone Function. Jacob K. Grohman, Robert J. Gorelick, Colin R. Lickwar, Jason D. Lieb, Brian D. Bower, Brent M. Znosko, Kevin M. Weeks. http://www.sciencemag.org/content/early/2013/03/06/science.1230715.