Jacob Schaefer

Titles:

Charles Allen Thomas Professor of Chemistry

Office Contact Information

Degrees:

Ph.D. University of Minnesota

Degrees:

B.S. Carnegie Institute of Technology

Office:

Louderman 340

Mailbox:

Campus Box 1134

Phone:

314-935-6844

Fax:

314-935-4481

Email:

jschaefer@wustl.edu

URL:

Group Site

Research specialization

Antibiotics; Bacterial Cell Walls; Biological Chemistry; Biophysical Chemistry; Magnetic Resonance; Materials Chemistry; Photorespiration; Photosynthesis; Physical Chemistry; Polymer Chain Packing; Polymer Chemistry; Polymer Dynamics; Protein Binding Sites

Research

Most of the recent applications of solid-state NMR to biological science have focused on the determination of the total structure of a peptide or protein in a micro-crystal, or a reconstituted model membrane, or a precipitated amyloid fibril or plaque. These applications have successfully adapted many of the popular multi-dimensional solution-state NMR experiments to the special demands of the solid state for samples that are either mechanically spun or aligned. For the last 30 years, our laboratory has been engaged in an effort to use solid-state NMR to detect (with a minimum of perturbation) stable isotope labels that have been introduced in vivo in bacteria, plants, insects, and shellfish. The goal is obviously not to determine a total structure but rather to connect partial local structure with biological function. We illustrate this strategy with an example: a correlation between photorespiration and glycine metabolism in intact leaves of Glycine max (soybeans). In this example, the principal NMR tool is rotational-echo double resonance (REDOR), whose use is illustrated in the figure.

Cross-polarization magic-angle ¹³C NMR spectrum of an intact lyophilized soybean leaf, (partially ¹⁵N-labeled by ¹⁵NH₄¹⁵NO₃) exposed for 6 minutes to ¹³CO₂ at 300 ppm (by volume). This is a difference spectrum resulting from the subtraction of the spectrum of an unexposed leaf. Each of the spectra in the difference resulted from the accumulation of 110,000 scans. The relative scaling of the two spectra was chosen to minimize the natural-abundance difference peaks between 10 and 30 ppm. Only peaks arising from the ¹³C label remain, and their integration gives an accounting of total ¹³C assimilation in the leaf during the labeling period. Two carbonyl-carbon difference peaks (in blue) are observed: one at 179 ppm (near the chemical shift of the carboxyl carbon of free glycine) and the other at 171 ppm (the characteristic chemical shift of the peptide carbonyl carbon of glycyl residues in helical local conformations). The 171-ppm peak and a 42-ppm methylene-carbon peak (both in red) decrease in intensity following a ¹³C{¹⁵N} dipolar evolution period for 1 msec (insets), indicating directly bonded ¹³C-¹⁵N pairs.

Awards & Honors:

2007, Schulich Lecturer, Technion, Haifa, Israel
2003, Laukien Prize of the Experimental NMR Conference
1995, Chair, Magnetic Resonance Gordon Research Conference
1987, Midwest Award of the American Chemical Society
1982, Monsanto Science and Technology Award
1980, Elected a Fellow in American Physical Society
1977, St. Louis Section Award of the American Chemical Society

Appointments

1986-present Charles Allen Thomas Professor of Chemistry, Washington University
1980-1986, Senior Monsanto Fellow, Monsanto Company, St. Louis
1974-1980, Monsanto Fellow, Monsanto Company
1964-1974, Senior Research Chemistry, Monsanto Company

Publications

J. Schaefer and E.O. Stejskal. "Carbon-13 Nuclear Magnetic Resonance of Polymers Spinning at the Magic Angle." J.Am. Chem. Soc., 98, 1031 (1976).

T. Gullion and J. Schaefer. "Rotational-Echo Double-Resonance NMR." J. Magn. Reson. 81, 196 (1989).

L. Cegelski and J. Schaefer. "Glycine Metabolism in Intact Leaves by in vivo ¹³C and ¹⁵N Labeling." J. Biol. Chem. 280, 39238-39245 (2005).

D. Stueber, A.K. Mehta, Z. Chen, K.L. Wooley, and J. Schaefer. "Local Order in Polycarbonate Glasses by ¹³C{¹⁹F} Rotational-Echo Double Resonance NMR." J. Polym. Sci. B, 44, 2760-2775 (2006).

S.J. Kim, L. Cegelski, D. Stueber, M. Singh, E. Dietrich, K.S.E. Tanaka, T.R. Parr, Jr., A.R. Far, and J. Schaefer. "Oritavancin exhibits dual mode of action to inhibit cell-wall biosynthesis in Staphylococcus aureus." J. Mol. Biol., 377, 281-193 (2008).

Courses Taught

List courses:

Chemistry 111, General Chemistry
Chemistry 421, Thermodynamics (old listing)
Chemistry 401, Physical Chemistry (quantum chemistry)
Chemistry 578, Magnetic Resonance

Curriculum Vitae:

Schaefer_CV.pdf