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Kim Chu-Young Assistant Professor Contact Information: Department of Biological Sciences National University of Singapore 14 Science Drive 4 Singapore 117543 Tel: 6516-1681 Fax: 6779-2486 E-mail: dbskcy@nus.edu.sg

Education and Training:

• Postdoctoral Associate (Chemistry) - Stanford University, U.S.A.
• Ph.D. (Chemistry) - University of Pennsylvania, U.S.A.
• M.S.E. (Bioengineering) - University of Pennsylvania, U.S.A.
• B.A. (Chemistry and Chemical Biology) - Cornell University, U.S.A. 

Research Areas:

Immunology, Autoimmune Disease, MHC, Drug Development, X-ray Crystallography

The Major Histocompatibility Complex (MHC) plays a central role in the human adaptive immune system. Employing HLA-DQ2 as a model system, we are investigating the molecular basis of MHC function, such as antigen loading, antigen presentation, and T-cell activation. We employ a broad range of methods including X-ray crystallography, chemical synthesis, and hydrogen-deuterium exchange coupled with mass spectrometry. Additionally, we are developing novel HLA-DQ2 blockers and gluten neutralizing molecules to serve as a therapeutic for celiac disease, an autoimmune-like disorder caused by gluten proteins found in wheat, rye, and barley.

a) X-ray crystal structure of HLA-DQ2 (grey) in complex with LQLQPFPQPELPY (yellow). HLA-DQ2 is a class II MHC protein associated with celiac disease and type I diabetes (Kim et al. PNAS 2004, 101, 4175-5179). b) MHC-peptide interaction involves multiple hydrogen bonds to the peptide main chain from conserved (blue) and polymorphic (red) MHC residues.

Collaboration:

• Dr. Yan Jie - Department of Physics, National University of Singapore (Singapore)
• Dr. Zeng Huaqiang - Department of Chemistry, National University of Singapore (Singapore)
• Dr. Ludvig M. Sollid - Institute of Immunology, University of Oslo (Norway)
• Dr. Stephen J. Benkovic - Department of Chemistry, Pennsylvania State University (U.S.A.)
• Dr. Andrew T. Koppisch - Bioscience Division, Los Alamos National Laboratory (U.S.A.)
• Dr. Weishuo Fang - Chinese Academy of Medical Sciences & Peking Union Medical College (China)

Selected Publications:

• Lars-Egil Fallang, Elin Bergseng, Kinya Hotta, Axel Berg-Larsen, Chu-Young Kim, Ludvig M. Sollid. Differences in the risk of celiac disease associated with HLA-DQ2.5 or HLA-DQ2.2 are related to sustained gluten antigen presentation. Nature Immunolgy 10, 1096-1101 (2009).

• David T. Fox, Kinya Hotta, Chu-Young Kim, Andrew T. Koppisch. The missing link in Petrobactin biosynthesis: AsbF encodes a (-)-3-dehydroshikimate dehydratase. Biochemistry (Rapid Reports) 47, 12251-12253 (2008).

• Andrew T. Koppisch, Kinya Hotta, David T. Fox, Christy E. Ruggiero, Chu-Young Kim, Timothy Sanchez, Srinivas Iyer, Cindy C. Browder, Pat J. Unkefer, Clifford J. Unkefer. Biosynthesis of the 3,4-dihydroxybenzoate moieties of petrobactin by Bacillus anthracis. Journal of Organic Chemistry 73, 5759-5765 (2008).

• Jiang Xia, Elin Bergseng, Burkhard Fleckenstein, Matthew Siegel, Chu-Young Kim, Chaitan Khosla, Ludvig M. Sollid. Cyclic and dimeric gluten peptide analogues inhibiting DQ2-mediated antigen presentation in celiac disease. Bioorganic & Medicinal Chemistry 15, 6565-6573 (2007).

• Yinyan Tang, Alice Y. Chen, Chu-Young Kim, David E. Cane, Chaitan Khosla. Structural and Mechanistic Analysis of Protein Interactions in Module 3 of the 6-Deoxyerythronolide B Synthase. Chemistry & Biology 14, 931-943 (2007).

• Yinyan Tang, Chu-Young Kim, Irimpan I. Mathews, David E. Cane, Chaitan Khosla.The 2.7-Å crystal structure of a 194-kDa homodimeric fragment of the 6-deoxyerythronolide B synthase. Proceedings of the National Academy of Sciences of the United States of America 103, 11124-11129 (2006).

• Alice Y. Chen, Nathan A. Schnarr, Chu-Young Kim, David E. Cane, Chaitan Khosla. Extender unit and acyl carrier protein specificity of ketosynthase domains of the 6-deoxyerythronolide B synthase. Journal of the American Chemical Society 128, 3067-3074 (2006).

• Elin Bergseng, Jiang Xia, Chu-Young Kim, Chaitan Khosla, Ludvig M. Sollid. Main chain hydrogen bond interactions in the binding of proline-rich gluten peptides to the celiac disease associated HLA-DQ2 molecule. Journal of Biological Chemistry 23, 21791-21796 (2005).

• Chu-Young Kim, Viktor Y. Alekseyev, Alice Y. Chen, Yinyan Tang, David E. Cane, Chaitan Khosla. Reconstituting modular activity from separated domains of 6-deoxyerythronolide B synthase. Biochemistry (Accelerated Publication) 43, 13892-13898 (2004).

• Chu-Young Kim, Hanne Quarsten, Elin Bergseng, Chaitan Khosla, Ludvig M. Sollid. Structural basis for HLA-DQ2 mediated presentation of gluten epitopes in celiac disease. Proceedings of the National Academy of Sciences of the United States of America 101, 4175-4179 (2004).

• Bartosz A. Grzybowski, Alexey V. Ishchenko, Chu-Young Kim, George Topalov, Robert Chapman, David W. Christianson, George M. Whitesides, Eugene I. Shakhnovich. Combinatorial computational method gives new picomolar ligands for a known enzyme. Proceedings of the National Academy of Sciences of the United States of America 99, 1270-1273 (2002).

• Chu-Young Kim, Douglas A. Whittington, Jeanne S. Chang, John Liao, Jesse A. May, David W. Christianson. Structural aspects of isozyme selectivity in the binding of inhibitors to carbonic anhydrases II and IV. Journal of Medicinal Chemistry 45, 888-893 (2002).

• Ryan D. Madder, Chu-Young Kim, Pooja P. Chandra, Jeffrey B. Doyon, Teaster A. Baird Jr., Carol A. Fierke, David W. Christianson, Judith G. Voet, Ahamindra Jain. Twisted amides inferred from QSAR analysis of hydrophobicity and electronic effects on the affinity of fluoroaromatic inhibitors of carbonic anhydrase. Journal of Organic Chemistry 67, 582-584 (2002).

• Chu-Young Kim, Pooja P. Chandra, Ahamindra Jain, David W. Christianson. Fluoroaromatic-fluoroaromatic interactions between inhibitors bound in the crystal lattice of human carbonic anhydrase II. Journal of the American Chemical Society 123, 9620-9627 (2001).

• Chu-Young Kim, Jeanne S. Chang, Jeffrey B. Doyon, Teaster T. Baird Jr., Carol A. Fierke, Ahamindra Jain, David W. Christianson. Contribution of fluorine to protein-ligand affinity in the binding of fluoroaromatic inhibitors to carbonic anhydrase II. Journal of the American Chemical Society 122, 12125-12134 (2000).

• Jeffrey B. Doyon, Elizabeth A. M. Hansen, Chu-Young Kim, Jeanne S. Chang, David W. Christianson, Ryan D. Madder, Judith G. Voet, Teaster A. Baird Jr., Carol A. Fierke, Ahamindra Jain. Linear free energy relationships implicate three modes of binding for fluoroaromatic inhibitors to a mutant of carbonic anhydrase II. Organic Letters 2, 1189-1192 (2000).

Updated on September 23, 2009.