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Faculty
 Jeffrey
C. Hoch
Director, Gregory P. Mullen NMR Structural Biology Facility
hoch@uchc.edu
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 UCHC 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)
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