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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:

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

Cell signaling and gene regulation in vertebrate development and cancer

Our lab focuses on the structural studies of selected pathways in cell signaling and gene regulation in vertebrate development and cancer. Protein structures conform to evolutionary genetic changes. As these molecular level changes are responsible for disorders and diseases, clear understanding of the nature of diseases mandates precise structure determination of the related proteins. We use X-ray crystallography, followed by biophysical, biochemical and functional characterization, to answer and address the biological questions.  

• Wnt signaling: b-catenin signaling pathway in the embryonic mouse mammary region coincides with initiation of mammary morphogenesis. Understanding the molecular mechanism of the development of mammary glands poses significant importance in breast cancer.

•  Planar cell polarity: Cell-cell interaction is very important in tissue formation and development. The most important question to be answered is how two cells communicate with each other during organogenesis.

• Kinases and cancer: Two protein tyrosine kinases, NPM/ALK and Brk play significant roles in lymphoma. The t(2;5) (p23;q35) translocation results in the formation of the NPM/ALK fusion gene. 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). Aberrant expression of these proteins plays a key role in malignant cell transformation of T lymphocytes.

• Methylated DNA binding proteins: DNA in mammalian genomes undergoes methylation at selected CpG islands. This chemical modification can lead to repression of transcription, which is of fundamental importance in development and cancer. Methylated DNA is often recognized by proteins that contain a conserved methyl-CpG binding domain (MBD) and represent an important class of chromosomal proteins. While the general properties of MBD proteins firmly tie these proteins to transcriptional repression, the important question regarding their biological action is still poorly understood.

Selected publications 2009-2005

• Suguna, B., Kim, C., Swaminathan, K. and Anand, G.S. (to be submitted soon). Crystal structures of apo protein kinase A (PKA) regulatory domain and its complexes with cAMP and Rp-cAMP: insights into inactivation of PKA.

• Liu, F., Kumar, S., Wei, S., Xia, N. and Swaminathan, K. (to be submitted soon). Crystal structure of Mycobacterium tuberculosis dodecin Rv1498A: biological implications and mechanism of assembly.

• Swaminathan, K. (to be submitted soon). Structure of Mycobacterium tuberculosis dodecin Rv1498A dodecin: lessons learned on unit-cell packing mimicry

• Vasudevan, D., Fu, A., Luan, S. and Swaminathan, K. (to be submitted soon). Crystal structure of Arabidopsis thaliana cyp38 precursor explains protein transportation to thylacoid lumen.

• Koh, C.Y., Kumar, S., Kazimirova, M., Nuttall, P.A., Radhakrishnan, U.P., Kim, S., Jagadeeswaran, P., Imamura, T., Mizuguchi, J., Iwanaga, S., Swaminathan, K., Kini, R.M. (submitted). Structure-function relationships and novel mechanism of thrombin inhibition by variegin: Design of potent thrombin inhibitors.

• Pal, K., Kumar, S., Sharma, S., Garg, S.K., Alam, M.S. Xu, H.E., Agrawal, P. and Swaminathan, K. (submitted). Crystal structure of full length mycobacterium tuberculosis H37RV glycogen branching enzyme: insights of N-terminal β-sandwich in substrate specificity and enzymatic activity.

• Zhang Q, Wang HY, Bhutani G, Liu X, Paessler M, Tobias JW, Baldwin D, Swaminathan K, Milone MC, Wasik MA. (2009). Lack of TNFalpha expression protects anaplastic lymphoma kinase-positive T-cell lymphoma (ALK+ TCL) cells from apoptosis. Proc. Natl. Acad. Sci. USA. 106, 15843-15848.

• Balakrishna, A.M., Saxena, A.M,, Mok, H.Y. and Swaminathan, K. (2009). Structural basis of typhoid: Salmonella typhi type IVb pilin (PilS) and cystic fibrosis transmembrane conductance regulator interaction. Proteins, 77, 253-261.

• Tan, T-C., Mijts, B.N., Swaminathan, K., Patel, P.K.C. and Divne, C. (2008). 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. J. Mol. Biol. 378, 852-870.

• Gopalan, G., Thwin, M.M., Gopalakrishnakone, P. and Swaminathan, K. (2007). Structural and pharmacological comparison of Daboiatoxin from Daboia russelli siamensis with viperotoxin F and vipoxin from other viper snakes. Acta Cryst. D63, 722-729.

• Sivakumar N., Li, N., Tang, J.W., Patel, B.K. and Swaminathan, K. (2006). Crystal structure of AmyA lacks acidic surface and provide insights into protein stability at poly-extreme condition. FEBS Lett, 580, 2646-2652.

• Gopalan, G., He, Z., Battaile, K.P., Luan, S. and Swaminathan, K. (2006). Structural comparison of oxidized and reduced FKBP13 from Arabidopsis thaliana. Proteins, 65, 789-795.

• Gopalan, G., Chopra, S., Ranganathan, A. and Swaminathan, K. (2006). Crystal structure of uncleaved L-aspartate-alpha-decarboxylase from Mycobacterium tuberculosis. Proteins, 65, 796-802.

• Lok, S.M., Rong, G., Rouault, M., Lambeau, G., Gopalakrishnakone, P. and Swaminathan, K. (2005). Structural comparison of Micropechis ikaheka phospholipase A₂ isoenzymes reveals a pharmacological motif on the C-terminus FEBS J., 272, 1211-1220.

Before 2005

• Gopalan, G., He, Z., Balmer, Y., Romano, P., Gupta, R., Heroux, A., Buchanan, B.B., Luan, S. and Swaminathan, K. (2004). Structural analysis uncovers a role for redox in regulating FKBP13, an immunophilin of the chloroplast thylakoid lumen Proc Natl Acad Sci., 101, 13945-13950.

• Saxena, S., Yuan, P., Dhar, S.K., Senga, T., Takeda, D., Robinson, H., Kornbluth, S., Dutta, A. and Swaminathan, K. (2004). A dimerized coiled-coil domain and an adjoining part of geminin interact with two sites on Cdt1 for replication inhibition  Molecular Cell, 15, 245-258.

• Zhang, D., Li, N., Lok, S.M., Zhang, L.H. and Swaminathan, K. (2003). Isomaltulose synthase (PalI) of Klebsiella sp. LX3. Crystal structure and implication of mechanism. J Biol Chem. 278, 35428-35434.

• Yuan, P., Jedd, G., Kumaran, D., Swaminathan, S., Shio, H., Hewitt, D. Chua, N-H.and Swaminathan, K. (2003). A HEX-1 crystal lattice required for Woronin body function in Neurospora crassa. Nature Structural Biology, 10, 264-270.

• Zhang D, Li N, Swaminathan K, Zhang LH. (2003). A motif rich in charged residues determines product specificity in isomaltulose synthase. FEBS Lett. 534, 151-155.

• Venkataramani, R., Swaminathan, K. and Marmorstein, R. (1998). Crystal structure of the CDK4/6 inhibitory protein p18^INK4c provides Insights into ankyrin-like repeat structure/function and tumor derived p16^INK4 mutations. Nature Structural Biology, 5, 74-81.

• Swaminathan, K., Flynn, P., Reece, R.J. and Marmorstein, R. (1997). Crystal structure of a PUT3-DNA complex reveals a novel mechanism for DNA recognition by a protein containing a Zn₂Cys₆ binuclear cluster. Nature Structural Biology, 4, 751-759.

 

Current lab members