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Dr.
ChulHee Kang
.jpg) 509-335-1409
chkang@wsunix.wsu.edu
Professor
of Biochemistry and Biophysics in School of Molecular Biosciences.
Director of BXRC Center.
Kang laboratory website:
http://kang7.chem.wsu.edu/~kang/
Research
I) The structural
changes of DNA induced by UV are responsible for lethal effects
of the skin cancer. The linkage between mutations in DNA repair
genes to some cancers has also become evident. We are trying to
identify the alteration in the structure of DNA upon UV-irradiation
and the means of recognition of altered DNA by various repair enzymes.
II) Calsequestrin(CSQ)
plays a vital role in regulating the Ca2+ release. Structures of
CSQ, juntin and Ryanodine receptor would provide an explanation
of the detailed mechanism by which cell accumulates and releases
Ca2+. This could lead us to a new therapeutic strategy for the cardiac
hypertrophy, which is the major source of the heart failure and
sudden death.
III) Structural
Studies of phenylpropanoid Biosynthetic Process. Lignins, lignans
and isoflavonoids are major constituents of vascular plants and
account for nearly 30% of the organic carbon circulating in the
biosphere. They play important roles in plant defense, helping
hosts discriminate between biological pathogens and symbiotic
non-pathogens. In addition to their physiological roles in plants,
these compounds have pronounced antimicrobial, antifungal, antiviral,
antioxidant and anticancer properties. Certain isoflavonoids and
lignans are used in medicinal applications, especially for the
clinical treatment of various cancers and in cancer prevention.
For these reasons, there is considerable interest in making these
compounds more generally available by defining and exploiting
the lignan and isoflavonoid biosynthetic pathways. These approaches
are seriously hampered, however, by a lack of detailed information
on the enzymes involved and the limited success in obtaining them
in significant amount. The goal of this project is thus to define
the structure-function relationships of these key proteins and
enzymes in lignan and isoflavonoid biosynthesis through high-resolution
X-ray structural analyses. The information gained from these studies
will be very useful for exploring the regulation of lignan and
isoflavonoid biosynthesis for ecological plant protection, and
for the industrial-scale regiospecific and stereospecific synthesis
of these pharmacologically active substances.
Selected
Publications
Youn, B., Camacho, R., Moinuddin, SGA, Lee, C., Davin, LB, Lewis,
NG & Kang, C. 2006. Crystal structures and catalytic mechanisms
of the Arabidopsis cinnamyl alcohol dehydrogenases AtCAD5 and AtCAD4.
Org. Biomol. Chem. 7:1687-1697.
Moinuddin, SGA, Youn, B, Bedgar, DA, Costa, MA, Helms, G, Kang,
C, Davin L, & Lewis, NG. 2006. Secoisolariciresinol Dehydrogenase:
Mode of Catalysis and Stereospecificity of Hydride Transfer in
Podophyllum peltatum. Org. Biomol Chem. 4:808-816.
Lee, S.M., Youn, B.H., Kim, C.S., Kim, J.S., Kang C., and Kim,
J. 2006. g-irradiation and doxorubicin in normal human cells show
cell cycle arrest via different pathways. Mol. Cell. 20:331-338.
Muir, T., Wilson-Rawls, J., Stevens, J., Rawls, A., Kang, C. & Skinner,
MK. 2006. Integration of CREB and bHLH Transcriptional Pathways
Through Heterodimerization of the Proteins. Molecular Endocrinology
(In press).
Tan, M-L, Kang C & Ichiye, T. 2006. The role of backbone stability
near Ala44 in the high reduction potential class of rubredoxins.
PROTEINS: Structure, Function and Genetics 62:708-714.
Kim, E., Tam, M., Siems, W.F., Kim, H., Kang, C. 2005. Effects
of drugs with muscle-related side effects and affinity for calsequestrin
on the calcium regulatory function of SR microsomes. Mol. Pharmacol.
68(6):1708-15.
Park, I.Y., Kim, E.-J., Park, H.J., Fields, K., Dunker, K.A., & Kang,
C. 2005. Interaction Between Cardiac Calsequestrin and Drugs with
Known Cardiotoxicity. Mol. Pharmacology 67:95-105.
Youn, B., Moinuldin, G.A.S., Davin, L.B., Lewis, N.G. & Kang,
C. 2005. Crystal structures of apo-form, binary and ternary complexes
of Podophyllum secoisolariciresinol dehydrogenase (SDH), an enzyme
involved in formation of health-protecting lignans and in plant
defense J. Biol. Chem. 280:12917-26.
Park, I.Y., Youn, B., Harley, J.L., Eidness, M.K., Smith, E.,
Ichiye, T. & Kang, C. 2004. The unique hydrogen bonded water
in the reduced form of Clostridium pasteurianum rubredoxin and
its possible role in electron transfer. J. Bio. Inor. Chem. 9:423-428.
Venclovas, C., Ginalski, K. & Kang, C. Sequence-structure
mapping errors in the PDB: OB-fold domains. 2004. Protein Science
13:1594-1602.
Park, H.-J., Suquet, C., Satterlee, J.D. & Kang, C. 2004.
Insights Into Signal Transduction Involving PAS Domain Oxygen Sensing
Heme Proteins from the X-ray Crystal Structure of E. coli Dos Heme
Domain (EcDosH) Biochemistry 16:2738-2746.
Park, H.-J., Park, I.-Y., Kim E.J., Wu, S., Youn, B., Fields,
K., Dunker, A.K., & Kang, C. 2004. Comparing skeletal and cardiac
calsequestrin structures and their calcium binding: a proposed
mechanism for coupled calcium binding and protein polymerization.
J. Biol. Chem. 279:18026-18033.
Park, I.Y., Eidness, M.K., Lin, I.J., Gebel, E.B., Youn, B., Harley,
J.L, Machonkin, T.E., Frederick, R.O., Markley, J.L., Eugene Smith,
E., Ichiye, T. & Kang, C. 2004. Crystallographic studies of
V44 mutants of Clostridium pasteurianum rubredoxin: Effects of
side chain size on reduction potential. PROTEINS: Structure, Function
and Genetics 57:618-624.
Rogers, S.W., Youn, B., Rogers, J.C., & Kang, C. 2004. Purification,
Crystallization and Preliminary Crystallographic Studies of the
Ligand Binding Domain of a Plant Vacuolar Sorting Receptor Acta
Crystallographica D6 2028-2030.
Park, H.-J., Hilsenbeck, J.L., Kim, H.J., Shuttleworth, W.A.,
Evans, J.N. and Kang, C. 2004. Structural Studies of Streptococcus
pneumoniae EPSP Synthase in Unliganded State, Tetrahedral intermediate
Bound State and S3P-GLP Bound State. J. Mol. Mic. 51:963-971.
Hilsenbeck, J.L., Park, H.-J., Chen, G., Youn, B., Postle, K.
and Kang, C. 2004. Crystal Structure of the Cytotoxic Bacterial
Protein Colicin B at 2.5 Å Resolution. J. Mol. Mic. 51:711-720.
Kang, C. 2003. Calsequestrin, Handbook of Metalloproteins series.
Vol. III, Wiley.
Kim, S.-J., Kim, M.-R., Bedgar, D.L., Moinuddin,
S.G.A., Cardenas, C.L., Davin, L.B., Kang, C. and Lewis, N.G. 2003.
Functional Reclassification of the Putative Cinnamyl Alcohol Dehydrogenase
(CAD) Multigene Family in Arabidopsis. PNAS, 1455-1460.
Ergenekan, K.E., Thomas, D., Fischer, J.T., Tan, M.-L., Eidsness,
M.K., Kang, C, and Ichiye, T. 2003. Prediction of Reduction Potential
Changes in Rubredoxin: A Molecular Mechanics Approach. Biophysical
Journal 85:2818-2829.
Min, T., Kasahara, T., Bedgar, D.L., Youn, B., Lawrence, P.K.,
Gang, D.R., Halls, S.C., Park, H.-J., Jacqueline, L., Hilsenbeck,
J.L., Davin, L.B., Lewis, N.G. and Kang, C. 2003. Crystal structures
of pinoresinol-lariciresinol and phenylcoumaran benzylic ether
reductases, and their relationship to isoflavone reductases. J.
Biol. Chem. 278:50714-50723.
Park, H.-J., Wu, S., Dunker, A.K. and Kang, C. 2003. Polymerization
of Calsequestrin: Implications for Ca2+ Regulation. J. Biol. Chem.
278:16176-16182.
Park, H.-J., Suquet, C., Savenkova, M.I., Satterlee, J.D. and
Kang, C. 2002. Crystallization and Preliminary X-ray Analysis of
the DOS Heme Domain: A new Heme Oxygen Sensor in E.
coli. Acta
Crystallographica D58:1504-1506.
Higgs, P., Letain, T.E. Merriam, K.K., Burke, N.S., Park, H.,
Kang, C., Postle, K. 2002. TonB Interacts with Non-receptor Proteins
at the Outer Membrane of Escherichia coli J. Bacteriology 184:1640-1648.
Park, H.-J., Ren, Y., Sinha, N., Taylor, J.-S. and Kang, C. 2002.
Crystal Structure of a DNA Decamer Containing a Thymine-dimer.
PNAS 99:15965-15970.
MacLennan, D.H. and Kang, C. 2002. Structure-Function Relationships
in Ca2+ Cycling proteins. J. Molecular and Cellular Cardiology
34:897-918.
Park, H.-J., Yang, C., Treff, N., Satterlee, J.D. and Kang. C.
2001. Crystal Structures of Components III and IV Glycera dibranchiata
Monomeric deoxy- and cyano-Hemoglobin. PROTEINS: Structure, Function
and Genetics 49:49-60.
Min, T., Ergenacan, C., Eidness, M., Ichiye, T. and Kang, C. 2001.
Mechanism of the Oxidation and Reduction Reaction in Rubredoxin.
Protein Science 10:613-621.
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