Charles G. Hoogstraten

Research Interests

The Hoogstraten laboratory studies biologically and biochemically important problems using techniques derived from biophysics and physical chemistry. Specifically, we are interested in the structure and function of RNA as studied using high-resolution nuclear magnetic resonance spectroscopy (NMR) in the liquid state, contemporary electron paramagnetic resonance (EPR) spectroscopy, and other techniques including solution thermodynamics.

One major area of interest is the study of the relationships between conformational dynamics, metal ion cofactors, and the catalytic mechanisms of catalytic RNA molecules (ribozymes). Solution-state NMR is unparalleled in its ability to give comprehensive site-specific information on the extent and timescales of dynamics of internal motions in macromolecules. We are interested in novel schemes to use this information to pick apart theconformational transitions that are a key part of the reaction coordinate for many ribozymes. Comparisons of NMR data with kinetic studies of ribozyme variants, or "dynamics-function" studies, provide particular insight into mechanism. As polyanions, catalytic RNA molecules often require divalent metal cation cofactors, which can play either structural or functional roles. We complement the NMR studies by using pulsed EPR to determine the structure of such metal ion sites in ribozymes and other RNA molecules. MORE

Recent Publications

JE Johnson, CG Hoogstraten. (2008) Extensive backbone dynamics in the GCAA RNA tetraloop analyzed using C-13 NMR spin relaxation and specific isotope labeling. J. Amer. Chem. Soc (Dec 10)130:16757-16769.

Julien, K.R., Sumita, M., Chen, P.-H., Laird-Offringa, I.A., & Hoogstraten, C.G. (2008) Conformationally Restricted Nucleotides as a Probe of Structure-Function Relationships in RNA. RNA 14, 1632-1643.

Hoogstraten, C.G. & Johnson, J.E., Jr. (2008) Metabolic Labeling: Taking advantage of bacterial pathways to prepare spectroscopically useful isotope patterns in proteins and nucleic acids. Concepts Magn. Reson. Ser. A 32, 34-55.

Hoogstraten CG, Sumita M. (2007) Structure-function relationships in RNA and RNP enzymes: Recent advances. Biopolymers. 87:317-328.

Vogt M, Lahiri S, Hoogstraten CG, Britt RD, DeRose VJ. (2006) Coordination environment of a site-bound metal ion in the hammerhead ribozyme determined by 15N and 2H ESEEM spectroscopy. J Am Chem Soc. 27;128(51):16764-70.

Johnson JE Jr, Julien KR, Hoogstraten CG. (2006) Alternate-site isotopic labeling of ribonucleotides for NMR studies of ribose conformational dynamics in RNA. J Biomol NMR. 35(4):261-74. MORE