1) 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.
2) 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.
3) 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.
Lewis KM, Ronish LA, Ríos E and Kang C. (2015) Characterization of Two Human Skeletal Calsequestrin Mutants Implicated in Malignant Hyperthermia and Vacuolar Aggregate Myopathy. JBC 290, 28665-28674.
Sattler SA, Wang X, Lewis KM, DeHan PJ, Park CM, Xin Y, Liu H, Xian M, Xun L and Kang C. (2015) Characterizations of Two Bacterial Persulfide Dioxygenases of the Metallo-β-lactamase Superfamily. JBC 290. 18914-18923. doi: 10.1074/jbc.M115.652537.
Cakir B, Tuncel A, Green AR, Koper K, Hwang SK, Okita TW, and Kang C (2015) Substrate binding properties of ADP-glucose pyrophosphorylase determined by using isothermal titration calorimetry. FEBS Letters 589, 1444-1449.
Hayes RP, Moural TW, Lewis KM, Onofrei D, Xun L and Kang C (2014) Structures of the inducer-binding domain of pentachlorophenol-degrading gene regulator PcpR from Sphingobium chlorophenolicum. Int. J. Mol. Sci. 15, 20736-20752.
Green AR, Lewis KM, Barr JT, JonesJP, Lu F, Ralph J, Vermerris W, Sattler SE & Kang C (2014) Determination of the Structure and Catalytic Mechanism of Sorghum bicolor Caffeic Acid O-Methyltransferase and the Structural Impact of Three brown midrib12 Mutations. Plant Physiology 165, 1440-1456.
Green, AR, Nissen MS, Kumar, GNM, Knowles NR and Kang C (2013) Characterization of Solanum tuberosum Multicystatin and the Significance of Core Domains. Plant Cell 25, 5043-5052.
Sanchez EJ, Hayes RP, Barr JT, Lewis KM, Webb BN, Subramanian AK, Nissen MS, Jones JP, Shelden EA, Sorg BA, Fill M, Schenk JO and Kang C (2013) Potential Role of cardiac calsequestrin in the lethal arrhythmic effects of cocaine. Drug and Alcohol Dependence 133, 344–351.
Hayes RP, Lewis KM, Xun L and Kang C (2013) Catalytic mechanism of 5-chlorohydroxyhydroquinone dehydrochlorinase from the YCII superfamily of largely unknown function. J Biol. Chem. 288, 28447-28456.
Wei Z, Sun K, Sandoval FJ, Cross JM, Christine Gordon C, Kang C, and Roje S (2013) Folate Polyglutamylation Stabilizes the Activity State of Mitochondrial Serine Hydroxymethyltransferases from Arabidopsis thaliana. Arch Biochem Biophys 536, 87-96.
Walker AM, Hayes RP, Youn B, Vermerris W, Sattler SE and Kang C (2013) Elucidation of the structure and reaction mechanism of Sorghum bicolor hydroxycinnamoyltransferase and its structural relationship to other CoA-dependent transferases and reductases. Plant Physiology 162, 640-651.
Hayes RP, Green AR, Nissen MS, Lewis KM, Xun L, Kang C. (2013) Structural characterization of 2,6-dichloro-p-hydroquinone 1,2-dioxygenase (PcpA) from Sphingobium chlorophenolicum, a new type of aromatic ring-cleavage enzyme. Mol Microbiol 88, 523-536.
Kang, C, Nissen, M, Sanchez, E and Milting, H. (2010) Potential adverse interaction of human cardiac calsequestrin. European Journal of Pharmacology. 646, 12-21.
Xun, L, Belchik, SM, Xun, R, Huang, Y, Zhou, H, Sanchez, E, Kang, C and Board, PP. (2010) S-Glutathionyl-(chloro) hydroquinone reductases: a novel class of glutathione transferases in bacteria and fungi. Biochemical Journal 428, 419-427.
Webb, BN, Ballinger JW, Kim E, Belchik S, Lam KS, Youn B, Nissen M, Xun L, and Kang C. (2010) Characterization of chlorophenol 4-monooxygenase (TftD) and NADH:FAD oxidoreductase (TftC) of Burkholderia cepacia AC1100. J Biol. Chem. 285, 2014-2027.
Nissen M, Kumar M, Youn B, Knowles DB, Lam KS, Ballinger WJ, Knowles NR and Kang C. (2009) Characterization of Potato Multicystatin and its Structural comparison with other Cystatins Plant Cell 21, 861-875.
Saballos A, Ejeta G, Sanchez E, Kang C, and Vermerris W (2009) A genome-wide analysis of the cinnamyl alcohol dehydrogenase family in sorghum (Sorghum bicolor (L.) Moench) identifies SbCAD2 as the Brown midrib6 gene. Genetics. 181, 783-795.
Nissen M, Youn, B, Knowles D, Ballinger J, Belchik S, Xun L and Kang C (2008) Crystal structures of NADH:FMN oxidoreductase (EmoB) at different stages of catalysis. J Biol. Chem. 283, 28710-20.
Muir, T., Wilson-Rawls, J., Stevens, J., Rawls, A., Kang, C. & Skinner, MK. (2008) Integration of CREB and bHLH transcriptional pathways through heterodimerization of the proteins. Molecular Reproduction and Development 75, 1637-1652.
Kim EJ, Youn B, Kemper L, Campbell C, Milting H, Varsanyi M & Kang C (2007) Biochemical analysis of human cardiac calsequestrin and its deleterious mutants. J Mol Biol. 373, 1047-57.
Cho MH, Corea OR, Yang H, Bedgar DL, Laskar DD, Anterola AM, Moog-Anterola FA, Hood RL, Kohalmi SE, Bernards MA, Kang C, Davin LB, Lewis NG. (2007) Phenylalanine biosynthesis in Arabidopsis thaliana: Identification and characterization of arogenate dehydratases. J Biol Chem. 282, 30827-35.
Hyatt DC, Youn, B, Zhao Y, Santhamma B, Coates RM, Croteau R. & Kang, C. (2007) Structure of limonene synthase, a simple model for terpenoid cyclase catalysis PNAS 104, 5360-5365.
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
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.