This proposal focuses on the development of solid state NMR methods for the characterization of 3D structures of proteins and peptides and the accomplishment of those structures. Peptide and protein structure will be demonstrated first with the short peptide MLF and then with protein G. The primary approach will be to use torsional constraints in crystalline samples for the local structure and distances for the long-range constraints. The research will employ innovative isotopic labeling schemes. Complex structures will be characterized with erythromycin/ribosome complex, the ribonucleotide reductase inhibitor complex and characterization of the potential low barrier hydrogen bond in lytic protease. The project with bound EA will dramatically push the limits of solid state NMR sensitivity. Negative labeling with 2H and 12C as well as the potential of using DNP (dynamic nuclear polarization) are presented. Protein dynamics will be characterized focusing on MLF and protein G, a complete characterization of dynamics in these systems is sought with 15N and 2H lineshapes and 2H relaxation. Method development will occur throughout this project to achieve the necessary goals of sensitivity, selectivity, assignments, and structural constraints.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Biophysical Chemistry Study Section (BBCB)
Program Officer
Wehrle, Janna P
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Massachusetts Institute of Technology
Internal Medicine/Medicine
Schools of Arts and Sciences
United States
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Jaroniec, Christopher P; MacPhee, Cait E; Bajaj, Vikram S et al. (2004) High-resolution molecular structure of a peptide in an amyloid fibril determined by magic angle spinning NMR spectroscopy. Proc Natl Acad Sci U S A 101:711-6
Veshtort, Mikhail; Griffin, Robert G (2004) High-performance selective excitation pulses for solid- and liquid-state NMR spectroscopy. Chemphyschem 5:834-50
Ladizhansky, Vladimir; Griffin, Robert G (2004) Band-selective carbonyl to aliphatic side chain 13C-13C distance measurements in U-13C,15N-labeled solid peptides by magic angle spinning NMR. J Am Chem Soc 126:948-58
Ladizhansky, Vladimir; Jaroniec, Christopher P; Diehl, Annette et al. (2003) Measurement of multiple psi torsion angles in uniformly 13C,15N-labeled alpha-spectrin SH3 domain using 3D 15N-13C-13C-15N MAS dipolar-chemical shift correlation spectroscopy. J Am Chem Soc 125:6827-33
Ramachandran, Ramesh; Ladizhansky, Vladimir; Bajaj, Vikram S et al. (2003) 13C-13C rotational resonance width distance measurements in uniformly 13C-labeled peptides. J Am Chem Soc 125:15623-9
Costa, Phillip R; Sun, Boqin; Griffin, Robert G (2003) Rotational resonance NMR: separation of dipolar coupling and zero quantum relaxation. J Magn Reson 164:92-103
Rovnyak, David; Filip, Claudiu; Itin, Boris et al. (2003) Multiple-quantum magic-angle spinning spectroscopy using nonlinear sampling. J Magn Reson 161:43-55
Reif, B; Griffin, R G (2003) 1H detected 1H,15N correlation spectroscopy in rotating solids. J Magn Reson 160:78-83
Rienstra, Chad M; Tucker-Kellogg, Lisa; Jaroniec, Christopher P et al. (2002) De novo determination of peptide structure with solid-state magic-angle spinning NMR spectroscopy. Proc Natl Acad Sci U S A 99:10260-5
Rienstra, Chad M; Hohwy, Morten; Mueller, Leonard J et al. (2002) Determination of multiple torsion-angle constraints in U-(13)C,(15)N-labeled peptides: 3D (1)H-(15)N-(13)C-(1)H dipolar chemical shift NMR spectroscopy in rotating solids. J Am Chem Soc 124:11908-22

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