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Address: NMR Core Facility, B291 CBRB, 285 Newton RoadIowa City, IA 52242Phone: (319) 384-3172
We are interested in molecular structure, function, dynamics,
interaction, and recognition as well as metabolic profiling and drug
discovery and development programs. The molecular targets could be
proteins, nucleic acids, oligosaccharides, drugs/metabolites, and/or
their complexes. One of the primary experimental tools used in our
laboratory is NMR spectroscopy. The Carver College of Medicine NMR Core
Facility has state of the art instrumentation including Bruker Avance
II 800 MHz, Varian Unity Inova 600 MHz, and Bruker Avance II 500 MHz
spectrometers. The Bruker 800 MHz spectrometer is equipped with a
sensitive TCI cryoprobe with pulse field gradients. The Bruker 800 and
500 MHz spectrometers are also equipped with automatic tuning and
matching and automatic sample exchanger, thus allowing us to run samples
continuously unattended day and night. This feature is particularly
valuable when screening a lot of samples, such as for sample
optimization or screen a compound library for discovering novel ligands
to bind to certain targets.</p>
<p>For protein structure determination, unlabeled protein could
be used first by collecting simple 1D 1H NMR spectra to assess the
spectral quality for suitability of NMR-based structural determination.
If needed, the protein sample could be optimized by conducting simple
buffer screening. Then, 15N-labeled sample is prepared, and 15N/1H HSQC
spectra are collected for the samples at different solution conditions
for further tuning the NMR spectral quality. If the sample is suitable
for structural determination, then 15N,13C-labeled protein is prepared
and a suite of backbone, side-chain, and NOESY experiments are collected
for backbone, side-chain, and NOE assignments. Finally, solution
structure could be calculated from NMR-derived distance and angular
restraints. Depending on protein size and spectral complexity,
different isotope-labeling schemes are often used for spectral
simplification and sensitivity enhancement and for aiding in NMR
Currently, we are working on structural determination of
proteins and carbohydrate receptors involved in (1) muscular dystrophy,
(2) bacterial quorum sensing, (3) microbial cell division, replication
and infection, (4) Ca+2 signaling, (5) immunity receptor activation by
endotoxin, (6) ubiquitin recognition by ubiquitin-binding proteins, and
(7) drug characterization and development. These research projects are
collaborated mainly with the faculty in the Carver College of Medicine.
Many of these research targets are involved in protein-ligand
interactions which are fundamentally important in cellular functions.
Therefore, the research is emphasized on the understanding structurally
how these proteins recognize their binding partners that could be
peptide, drug, carbohydrate, or another protein, and how they perform
the biological functions.
We are also interested in protein modeling and intermolecular docking,
e.g. by HADDOCK in order to build 3D models based on NMR and other
The Carver College of Medicine NMR Core Facility can provide the
Liping Yu, Brian D. Fink, Judith A. Herlein, Christine L. Oltman, Kathryn G. Lamping, and William I. Sivitz. (2014) Dietary fat, fatty acid saturation and mitochondrial bioenergetics. J. Bioenerg. Biomembr., 46, 33-44.
Takako Yoshida-Moriguchi, Tobias Willer, Mary E. Anderson, David Venzke,
Tamieka Whyte, Francesco Muntoni, Hane Lee, Stanley F. Nelson, Liping
Yu, and Kevin P. Campbell. (2013) SGK196 is a glycosylation-specific
O-mannose kinase required for dystroglycan function. Science, 341, 896-899.
Natasha Pashkova, Lokesh Gakhar, Stanley C. Winistorfer, Anna B.
Sunshine, Matthew Rich, Maitreya J. Dunham, Liping Yu, and Robert C.
Piper. (2013) The yeast Alix homolog Bro1 functions as a ubiquitin
receptor for protein sorting into multivesicular endosomes. Developmental Cell, 25, 520-533.
Liping Yu, Brian D. Fink, Judith A. Herlein, and William I. Sivitz. (2013) Mitochondrial function in diabetes: Novel methodology and new insight. Diabetes, 62, 1833-1842.
Liping Yu, Rachel L. Phillips, DeSheng Zhang, Athmane Teghanemt,
Jerrold P. Weiss, and Theresa L. Gioannini. (2012) NMR studies of
hexaacylated endotoxin bound to wild-type and F126A mutant MD-2 and
MD-2/TLR4 ectodomain complexes. J. Biol. Chem., 287, 16346-16355.
Post, D. M. B.*, Yu, L.*, Krasity, B. C.* (*these authors contributed
equally), Choudhury, B., Mandel, M. J., Brennan, C. A., Ruby, E. G.,
McFall-Ngai, M. J., Gibson, B. W., and Apicella, M. A. (2012) O-antigen
and core carbohydrate of Vibrio fischeri lipopolysaccharide: composition and analysis of their role in Euprymna scolopes light organ colonization. J. Biol. Chem.,287, 8515-8530.
Kei-ichiro, I, Yoshida-Moriguchi, T., Hara Y., Anderson, M. E., Yu, L., Campbell K. P. (2012) Dystroglycan function requires xylosyl- and glucuronyltransferase activities of LARGE. Science, 335, 93-96.
Qiu, Jiang; Yu, Liping; and Kirsch, Lee E. (2011) Estimated pKa values for specific amino acid residues in daptomycin. J. Pharm. Sci., 100, 4225-4233.
Feldkamp, Michael D.; Yu, Liping; and Shea, Madeline A. (2011)
Structural and energetic determinants of apo calmodulin binding to the
IQ-motif of the NaV1.2 voltage-dependent sodium channel. Structure, 19, 733-747.
O'Donnell, S. E., Yu, L., Fowler, C. A., & Shea, M. A. (2011)
Recognition of beta-calcineurin by the domains of calmodulin:
thermodynamic and structural evidence for distinct roles. Proteins, 79,
Pashkova, N., Gakhar, L., Winistorfer, S. C., Yu, L., Ramaswamy, S.,
& Piper, R. C. (2010) WD40 repeat propellers define a ubiquitin
binding domain that regulates turnover of F-box proteins. Mol. Cell, 40,
Feldkamp, M. D., O’Donnell, S. E., Yu, L., & Shea, M. A. (2010)
Allosteric effects of the antipsychotic drug trifluoperazine on the
energetics of calcium binding by calmodulin. Proteins, 78, 2265-2282.
Barghorn, Stefan; Hillen, Heinz; Edalji, Rohinton; Barrett, Leo;
Richardson, Paul; Yu, Liping; Olejniczak, Edward; Harlan, John; Holzman,
Thomas. (2010) Amyloid-beta peptide analogs: oligomerization,
stability, and immunogenicity. PCT Int. Appl., 233pp. WO 2010011947 A2.
Yoshida-Moriguchi, T., Yu, L., Stalnaker, S. H., Davis, S.,
Kunz, S., Madson, M., Oldstone, M. B. A., Schachter, H., Wells, L.,
& Campbell, K. P. (2010) O-mannosyl phosphorylation of
alpha-dystroglycan is required for laminin binding. Science, 327,
Piazza, M., Yu, L., Teghanemt, A., Gioannini, T., Weiss, J., & Peri,
F. (2009) Evidence of a specific interaction between new synthetic
antisepsis agents and CD14. Biochemistry, 48, 12337-12344.
Yu, L., Edalji, R., Harlan, J. E., Holzman, T. F., Pereda-Lopez, A.,
Labkovsky, B., Hillen, H., Barghorn, S., Ebert, U., Richardson, P.,
Miesbauer, L., Solomon, L., Bartley, D., Walter, K., Johnson, R. W.,
Hajduk, P. J., & Olejniczak, E. T. (2009) Structural
characterization of a soluble amyloid beta-peptide oligomer.
Biochemistry, 48, 1870-1877.
Hillen, Heinz; Labkovsky, Boris; Olejniczak, Edward T.; Barghorn, Stefan; Holzman, Thomas F.; Harlan, John E.; Edalji, Rohinton P.; Pereda-Lopez, Ana; Yu, Liping; Ebert, Ulrich M. (2009) Methods of preparation of recombinant forms of human beta-amyloid protein and uses of these proteins. United States Patent Application, 20090214515.
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