
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 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
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.
Recent Publications