Areas of Interest
Our laboratory works on problems related to the physical basis
for the biological activity of proteins. Broadly, this includes
their structure, dynamics, stability, and interactions with
other molecules. Some specific questions we are interested in
include:
The relationship of protein dynamics and structure to
biological activity. An example is the role of structure and
dynamics in the interaction between prolactin and the prolactin
receptor. Prolactin is involved in hundreds of biochemical
pathways, and has been shown to be involved in cancer
(expression levels of both prolactin and its receptor are
elevated in some forms of breast cancer). Understanding the
physical basis for prolactin-receptor interaction will aid the
search for molecules that inhibit or enhance the signaling
functions of prolactin.
In collaboration with Professor Choukri Ben-Mamoun we are
investigating the structural biology of Plasmodium falciparum,
the parasite that causes malaria. Despite the devastating impact
of malaria on the developing world, cheap, safe, and effective
treatments for malaria remain elusive. We are solving the
structure of an enzyme that is essential for the survival of
Plasmodium that has no homologs in mammals, and thus is
potentially an important drug target. We plan to solve the
structures of additional Plasmodium proteins.
In collaboration with Professors Asis Das and Jun Li we are
investigating the metabolome (the small biologically active
molecules in the cell) of embryonic stem cells. We use nuclear
magnetic resonance (NMR) spectroscopy, which is capable of
measuring the concentration of metabolites in intact cell
suspensions. Quantifying the metabolome will help us to
understand the biochemical pathways that are responsible for
maintaining pluripotency of stem cells and for differentiation.
We employ a variety of physical and computational methods,
especially NMR, and also circular dichroism, fluoresence, and
ultraviolet/visible absorption spectroscopies, measurements of
water activity, differential and isothermal titration
calorimietry, non-Fourier spectrum analysis, and molecular
dynamics simulations.
The NMR resources at the UConn Health Center are outstanding,
and include spectrometers operating at 400, 500 and 600 MHz. The
latter two instruments are equipped with state-of-the-art
cryogenically cooled probes. The Health Center was recently
awarded a $2 million NIH grant for an 800 MHz NMR spectrometer,
which will be operational in late 2008.
Selected Publications
An automated tool for maximum entropy reconstruction of
biomolecular NMR spectra. Mobli M, Maciejewski MW, Gryk MP, Hoch
JC, Nature Meth. 4, 3-4 (2007)
NMR Data Processing using Iterative Threshholding and Minimum
l1-norm reconstruction, Alan S. Stern, David Donoho, and Jeffrey
C. Hoch, J. Magn. Reson. 188, 295-300 (2007)
D 13C-detected CH3-TOCSY applied to selectively protonated
proteins: A facile route to resonance assignment and global fold
determination, John B. Jordan, Helena Kovacs, Yuefeng Wang,
Mehdi Mobli, Rensheng Luo, Clemens Anklin, Jeffrey C. Hoch, and
Richard W. Kriwacki, J. Am. Chem. Soc. 128, 9199-9128 (2006)
Spectral reconstruction methods in fast NMR: reduced
dimensionality, random sampling and maximum entropy. Mobli M,
Stern AS, Hoch JC. J. Magn. Reson. 182, 96-105 (2006)
Non-uniformly Sampled Double-TROSY hNcaNH Experiments for NMR
Sequential Assignments of Large Proteins, Frueh DP, Sun ZY,
Vosburg DA, Walsh CT, Hoch JC, Wagner G., J. Am. Chem. Soc. 128,
5757-5763 (2006)
Fast Assignment of 15N-HSQC Peaks using High-Resolution 3D
HNcocaNH Experiments with Non-Uniform Sampling, Zhen-Yu J. Sun,
Dominique P. Frueh, Philipp Selenko, Jeffrey C. Hoch, and
Gerhard Wagner, J. Biomol. NMR 33, 43-50 (2005)
Solution Structure of Human Prolactin, Kaare Teilum, Jeffrey
C. Hoch, Vincent Goffin, Sandrina Kinet, Joseph A. Martial, and
Birthe B. Kragelund, J. Mol. Bio. 351, 810-823 (2005)
High-resolution aliphatic side-chain assignments in 3D HCcoNH
experiments with joint H–C evolution and non-uniform sampling,
Zhen-Yu J. Sun, Sven G. Hyberts, David Rovnyak, Sunghyouk Park,
Alan S. Stern, Jeffrey C. Hoch and Gerhard Wagner, J. Biomol.
NMR 32, 55-60 (2005)
Bayesian Restraint Potentials for Consistent Inference of
Biomolecular Structure from NMR Data, Jeffrey C. Hoch and Alan
S. Stern, in “Structure, Dynamics and Function of Biological
Macromolecules and Assemblies”, J. Puglisi, ed. IOS Press,
Amsterdam (2005) |
