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Research Interest:
My group is actively engaged in the determination of biomolecular
structures and functions using multi-dimensional NMR spectroscopy
and other biophysical techniques (such as CD, fluorescence,
Biosensor, etc.). During
the past years, we have made considerable progress in understanding
the the stability, folding, structure, and peptide binding
specificity of the SH3 and SH2 domains of Btk, a tyrosine
kinase that is involved in X-Linked agammaglobulinemia
(XLA) and B cell development. The
success of this work depended
heavily on the protein cloning, expression, purification,
and NMR structural study ability of this group.
In addition to the structural and functional studies of Btk,
we have determined the solution conformation of the propeptide
domain of factor IX and the predicted a-helix
region of HIV-1 integrae. We
have also determined the relationship between local helix
contents and RNA binding activity of the N-terminal leucine-repeat
region of hepatitis delta antigen. For
the DNA/RNA structural studies, we have determined the hydration
and solution structures of the DNA/RNA hybrid duplexes, [d(CGC)r(aaa)d(TTTGCG)]2 and
[d(CGC)r(amamam)d(TTTGCG)]2. We
have also developed a new synthetic method to synthesize 15N-
and 13C-labeled nucleosides which can be used
in the protein/DNA complex structural studie.
Selected Publications:
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Wu KP, Wu CW, Tsao YP, Kuo TW, Lou YC, Lin CW,
Wu SC, Cheng JW*. Structural basis of a flavivirus recognized
by its neutralizing antibody: solution structure of the domain
III of the Japanese encephalitis virus envelope protein Journal
of Biological Chemistry 278, 46007-46013 (2003).
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Pai MT, Yang CS, Tzeng SR, Wang C, Cheng JW*.
1H, 15N and 13C resonance assignments of the tetratricopeptide
repeat (TPR) domain of hSGT Journal of Biomolecular NMR 26, 381-382
(2003).
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M.T. Pai, K.C. Huang, S.R. Tzeng, and J.W. Cheng*,
1H, 15N and 13C resonance assignments of the SH2 domain of Bruton's
tyrosine kinase Journal of Biomolecular NMR 24, 163-164 (2002).
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F.T. Lung, J.Y. Tsai, S.Y. Wei, C. Chen, P.P.
Roller, and J.W. Cheng, Novel peptide inhibitors for Grb2 SH2
domain and their detection by surface plasmon resonance Journal
of Peptide Research 60, 143-149 (2002).
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M.L. Jain, Y.P. Tsao, N.L. Ho, and J.W. Cheng*,
A Facile Synthesis of [N1, NH2-15N2]Adenine, [N3, NH2-15N2]Adenine
and [N1, N3, NH2-15N2]Adenine Journal of Organic Chemistry 60,
6472-6475 (2001).
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Y.P. Tsao, L.Y. Wang, S.T. Hsu, M.L. Jain, S.H.
Chou, W.C. Huang, and J.W. Cheng*, The Solution Structure of
[d(CGC)r(amamam)d(TTTGCG)]2 Journal of Biomolecular NMR 21, 209-220
(2001).
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S.R. Tzeng, M.T. Pai, F.T. Lung, C.W. Wu, P.P.
Roller, B. Lei, C.J. Wei, S.C. Tu, S.H. Chen, W.J. Soong, and
J.W. Cheng*, Stability and Peptide Binding Specificity of BTK
SH2 Domain: Molecular Basis for X-Linked Agammaglobulinemia Protein
Science 9, 2377-2385 (2000).
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Y.C. Lou, I.J. Lin, M.T. Pai, and J.W. Cheng*,
Solution Structure of an N-Capping Peptide from the N-terminal
Leucine-Repeat Region of Hepatitis Delta Antigen Archives of
Biochemistry and Biophysics 377, 219-227 (2000).
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S.T. Hsu, M.T. Chou, and J.W. Cheng*, The Solution
Structure of [d(CGC)r(aaa)d(TTTGCG)]2: Hybrid Junctions Flanked
by DNA Duplexes Nucleic Acids Research 28, 1322-1331 (2000).
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S.T. Hsu, M.T. Chou, S.H. Chou, W.C. Huang and
J.W. Cheng*, Hydration of [d(CGC)r(aaa)d(TTTGCG)]2 Journal of
Molecular Biology 295, 1129-1137 (2000).
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S.R. Tzeng, Y.C. Lou, M.T. Pai, and J.W. Cheng*,
Solution Structure of the BTK SH3 Domain Complexed with a Proline-Rich
Peptide from p120cbl Journal of Biomolecular NMR 16, 303-312
(2000).
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Y.C. Lou, F.T. Lung, M.T. Pai, S.R. Tzeng, S.Y.
Wei, P.P. Roller, and J.W. Cheng*, Solution Structure and Dynamics
of a Nonphosphorelated Cyclic Peptide Inhibitor for the Grb2
SH2 Domain Archives of Biochemistry and Biophysics 372, 309-314
(1999).
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S.H. Chou, Y.Y. Tseng, Y.R. Chen, and J.W. Cheng,
Structural Studies of Symmetric DNA Undecamers Containing Non-Symmetrical
Sheared (PuGAPu):(PyGAPy) Motifs Journal of Biomolecular NMR 14, 157-167 (1999).
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I.J. Lin, Y.C. Lou, M.T. Pai, H.N. Wu and J.W.
Cheng*, Solution Structure and RNA Binding Activity of the N-terminal
Leucine-Repeat Region of Hepatitis Delta Antigen PROTEINS: Structure,
Function, and Genetics 37, 121-129 (1999).
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