Back

Curriculum vitae

Laboratory of Macromolecular
X-ray Crystallography

Contact Information:
Dept of Biological Sciences
National University of Singapore
Blk S3, #04-15,
Science Drive 4,
Singapore 117543
Tel: 65167932
Fax: 67792486
Email: dbsks@nus.edu.sg

Education:

7/1978-5/1981B.Sc. (Physics with distinction) Madras Univ., India

8/1981-6/1983M.Sc. (Physics with distinction) Madras Univ., India

1/1984-11/1989Ph.D. in Crystallography - Indian Inst. of Technology, Bombay, India

Post-doctoral training:

11/1989 - 5/1995   Department of Chemistry, Univ. of Pennsylvania, Philadelphia, USA (with Prof. Donald Voet, the author of the famous Voet & Voet Biochemistry textbook)

5/1995 - 12/1997     The Wistar Institute, Philadelphia, USA (with Prof. Ronen Marmorstein)

See my full CV

Proteins and nucleic acids are mostly responsible for all the biochemical pathways and diseases. As the function of a protein is related to its three dimensional structure, well resolved structures lead to very clear understanding of the functions of these molecules. X-ray crystallography is a powerful methodology to determine macromolecular structures at atomic resolution. These structures confirm evolutionary changes in the primary structure of a given protein from related species, through random mutations. As these mutations lead to genetic disorders and diseases of molecular level, clear understanding of the nature of these diseases depends upon precise structure determination of the concerned proteins.

Selected current projects

• Structures of non-canonical Wnt signaling pathway proteins: Mammary glands and skin appendages, like hair follicles and teeth, develop from the surface epithelium and underlying mesenchyme. Activation of the canonical WNT/b-catenin signaling pathway in the embryonic mouse mammary region coincides with initiation of mammary morphogenesis, and the formation of all types of hair follicle placode requires signaling through a WNT/b-catenin pathway. The development of hair follicle tumors, resulting from uncontrolled activation of the WNT/b-catenin pathway, underscores the importance of delineating the mechanisms by which endogenous WNT signals normally operate. In the same line, understanding the molecular mechanism of the development of mammary glands poses significant importance in breast cancer. Thus, the manipulation of WNT/b-catenin signaling could provide a powerful therapeutic tool. We are working on the crystal structure determination of selected canonical and non-canonical Wnt signaling pathway proteins. 

• Kinases and lymphoma: Two protein tyrosine kinases, NPM/ALK and Brk play significant roles in lymphoma, a diverse group of malignancy. The t(2;5) (p23;q35) translocation results in the formation of the NPM/ALK fusion gene and aberrant expression of NPM/ALK plays a key role in malignant cell transformation of T lymphocytes. Brk (or PTK6 and its murine homolog Sik) is a member of the Frk family of intracellular tyrosine kinases (also distantly related to src kinases). Brk is induced in normal T lymphocytes after their activation. It is constitutively expressed in a nucleus-localized and continuously activated form in malignant T cells and Epstein-Barr virus (EBV)-transformed and lymphoma-derived B cells and plays a key role in their proliferation and survival. This proposal aims to study the structure-function relationship of these two important proteins and their involvement in lymphoma.  

Selected publications

1. Crystal structure of a PUT3-DNA complex reveals a novel mechanism for DNA recognition by a protein containing a Zn₂Cys₆ binuclear cluster Swaminathan, K., Flynn, P., Reece, R.J. and Marmorstein, R. (1997). Nature Structural Biology, 4, 751.

2. rystal structure of the CDK4/6 inhibitory protein p18^INK4c provides Insights into ankyrin-like repeat structure/function and tumor derived p16^INK4 mutations. Venkataramani, R., Swaminathan, K. and Marmorstein, R. (1998). Nature Structural Biology, 5, 74.

3. A motif rich in charged residues determines product specificity in isomaltulose synthaseZhang, D.H., Li, N., Swaminathan, K. and Zhang, L.H. (2003). FEBS Lett., 534, 151.

4. A HEX-1 crystal lattice required for Woronin body function in Neurospora crassa. Yuan, P., Jedd, G., Kumaran, D., Swaminathan, S., Shio, H., Hewitt, D. Chua, N-H.and Swaminathan, K. (2003). Nature Structural Biology, 10, 264.

5. Isomaltulose synthase (PalI) of Klebsiella sp. LX3: crystal structure and implication of mechanism Zhang, D-H., Li, N., Lok, S-M., Zhang, L-H. and Swaminathan, K. (2003). J. Biol. Chem., 278, 35428.

6. A dimerized coiled-coil domain and an adjoining part of geminin interact with two sites on Cdt1 for replication inhibition Saxena, S., Yuan, P., Dhar, S.K., Senga, T., Takeda, D., Robinson, H., Kornbluth, S., Dutta, A. and Swaminathan, K. (2004). Molecular Cell, 15, 245.

7. Structural analysis uncovers a role for redox in regulating FKBP13, an immunophilin of the chloroplast thylakoid lumen. Gopalan, G., He, Z., Balmer, Y., Romano, P., Gupta, R., Heroux, A., Buchanan, B.B., Luan, S. and Swaminathan, K. (2004). Proc Natl Acad Sci., 101, 13945.

8. Structural comparison of Micropechis ikaheka phospholipase A₂ isoenzymes reveals a pharmacological motif on the C-terminus. Lok, S.M., Rong, G., Rouault, M., Lambeau, G., Gopalakrishnakone, P. and Swaminathan, K. (2005). FEBS J., 272, 1211.

9. Crystal structure of AmyA lacks acidic surface and provide insights into protein stability at poly-extreme condition. Sivakumar N., Li, N., Tang, J.W., Patel, B.K. and Swaminathan, K. (2006). FEBS Lett, 580, 2646.

10. Structural comparison of oxidized and reduced FKBP13 from Arabidopsis thaliana. Gopalan, G., He, Z., Battaile, K.P., Luan, S. and Swaminathan, K. (2006). Proteins, 65, 789.

11. Crystal structure of uncleaved L-aspartate-alpha-decarboxylase from Mycobacterium tuberculosis. Gopalan, G., Chopra, S., Ranganathan, A. and Swaminathan, K. (2006). Proteins, 65, 796.

12. Structural and pharmacological comparison of Daboiatoxin from Daboia russelli siamensis with viperotoxin F and vipoxin from other viper snakes. Gopalan, G., Thwin, M.M., Gopalakrishnakone, P. and Swaminathan, K. (2007). Acta Cryst. D63, 722.

13. Crystal structure of the polyextremophilic α-amylase AmyB from Halothermothrix orenii: details of a productive enzyme-substrate complex and an N domain with a role in binding raw starch. Tan, T-C., Mijts, B.N., Swaminathan, K., Patel, P.K.C. and Divne, C. (2008). J. Mol. Biol. (in press).

 Current lab members