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Curriculum vitae
sivaraman J SIVARAMAN
(Assistant Professor)

Contact Information:
Department of Biological Sciences
National University of Singapore
Science Drive 4
Singapore 117543
Tel: 6516 1163
Fax: 6779 5671
E-mail: dbsjayar@nus.edu.sg

Research Areas
Structural Biology (Protein crystallography), Biophysical studies and Bio-Informatics

Research Focus
Proteins are important biological macromolecules playing vital and integral roles in all living systems. Proteins are implicated in many diseases, including infectious diseases, in animals as well as humans. X-ray crystallography is a robust experimental technique, which enables us to determine three-dimensional structures of proteins, and thus to understand their functional roles. So it is important to study proteins that may play in the diseases. This can be achieved by the structural and structure based functional (mutagenesis and biophysical / biochemical) studies. Our laboratory focuses on studies of a number of proteins that play active roles in various diseases.

One of our research objectives is the study of bacterial RNA modifying enzymes such as Pseudouridine synthases and Methyltransferases that perform post-transcriptional modifications of cellular RNA. These enzymes are implicated in a variety of functions ranging from regulation of the accurate functioning of the ribosome to the acquisition of antibiotic resistance by microbes.

Our second research objectives are directed towards understanding of host-pathogen interactions and the early phase of defense and innate immune response in the host. This project will encompass studies of molecular mechanisms of bacterial and viral pathogenesis in the context of the disease process. To this end, we are investigating a class of virulence-factor delivery system in gram-negative bacteria called the Type Three Secretion System (TSSS). We are also carrying out studies on proteins from WSSV (White-spot syndrome virus), a virus that has a severe scourge of the shrimp aquaculture industry.

In addition we are also conducting collaborative projects with other groups, focusing on targeted structural and functional studies on disease relevant proteins such as Cancer relevant kinases, proteases and toxins. 

The long-term goal of our group is to illuminate outstanding challenges in the area of various diseases (including infectious diseases) and to provide new avenues for addressing them towards drug design

Selected Publications

  • Liu Y, Li Z, Lin Q, Kosinski J, Seetharaman J, Bujnicki JM, Sivaraman J* Hew CL*. Structure and Evolutionary Origin of Ca-Dependent Herring Type II Antifreeze Protein. PLoS ONE. (2007).2:e548.

  • Sunita S, Purta E, Durawa M, Tkaczuk KL, Swaathi J, Bujnicki JM, Sivaraman J*. Functional specialization of domains tandemly duplicated within 16S rRNA methyltransferase RsmC.
    Nucleic Acids Research.     (2007), Jun 27 [Epub ahead of print]

  • Zheng J, Li N, Tan YP, Sivaraman J, Mok YK, Mo ZL, Leung KY. EscC is a chaperone for the Edwardsiella tarda type III secretion system putative translocon components EseB and EseD. Microbiology. (2007).153(6):1953-62.

  • Jobichen C, Li M, Yerushalmi G, Tan YW, Mok YK, Rosenshine I, Leung KY, Sivaraman J*. Structure of GrlR and the implication of its EDED motif in mediating the regulation of type III secretion system in EHEC. PLoS Pathog. (2007).3(5):e69.

  • Tang X, Wu J, Sivaraman J*, Hew CL*. Crystal structures of major envelope proteins VP26 and VP28 from white spot syndrome virus shed light on their evolutionary relationship. J Virol. (2007) 81 (12): 6709-17.

  • Liu Y, Wu J, Song J, Sivaraman J, Hew CL. Identification of a novel nonstructural protein, VP9, from white spot syndrome virus: its structure reveals a ferredoxin fold with specific metal binding sites.
    J Virol.     (2006).80(21):10419-27.

  • Sunita S, Zhenxing H, Swaathi J, Cygler M, Matte A, Sivaraman J*. Domain organization and crystal structure of the catalytic domain of E.coli RluF, a pseudouridine synthase that acts on 23S rRNA.
    J Mol Biol.     (2006). 359(4):998-1009.

  • Sivaraman J, Myers RS, Boju L, Sulea T, Cygler M, Jo Davisson V, Schrag JD. Crystal structure of Methanobacterium thermoautotrophicum phosphoribosyl-AMP cyclohydrolase HisI. Biochemistry. (2005). 44(30):10071-80.

  • Sivaraman J, Iannuzzi P, Cygler M, Matte A. Crystal structure of the RluD pseudouridine synthase catalytic module, an enzyme that modifies 23S rRNA and is essential for normal cell growth of Escherichia coli. J Mol Biol. (2004).335(1):87-101.

  • Sivaraman J, Li Y, Banks J, Cane DE, Matte A, Cygler M. Crystal structure of Escherichia coli PdxA, an enzyme involved in the pyridoxal phosphate biosynthesis pathway. J Biol Chem. (2003). 278(44):43682-90.

  • Matte A, Sivaraman J, Ekiel I, Gehring K, Jia Z, Cygler M. Contribution of structural genomics to understanding the biology of Escherichia coli. J Bacteriol. (2003).185(14):3994-4002.

  • Pauly TA, Sulea T, Ammirati M, Sivaraman J, Danley DE, Griffor MC, Kamath AV, Wang IK, Laird ER, Seddon AP, Menard R, Cygler M, Rath VL. Specificity determinants of human cathepsin s revealed by crystal structures of complexes. Biochemistry. (2003.42(11):3203-13.

  • Chowdhury SF, Sivaraman J, Wang J, Devanathan G, Lachance P, Qi H, Menard R, Lefebvre J, Konishi Y, Cygler M, Sulea T, Purisima EO. Design of noncovalent inhibitors of human cathepsin L. From the 96-residue proregion to optimized tripeptides. J Med Chem. (2002). 45(24):5321-9.

  • Rangarajan ES, Sivaraman J, Matte A, Cygler M. Crystal structure of D-ribose-5-phosphate isomerase (RpiA) from Escherichia coli. Proteins. (2002.48(4):737-40.

  • Barbosa JA, Sivaraman J, Li Y, Larocque R, Matte A, Schrag JD, Cygler M. Mechanism of action and NAD+-binding mode revealed by the crystal structure of L-histidinol dehydrogenase.
    Proc Natl Acad Sci     USA.(PNAS) (2002.99(4):1859-64.

  • Sivaraman J, Sauve V, Larocque R, Stura EA, Schrag JD, Cygler M, Matte A. Structure of the 16S rRNA pseudouridine synthase RsuA bound to uracil and UMP. Nature Structural Biology (2002)9(5):353-8. (A'News and Views' Comments on the above paper. Chips off the old block by E.G.Mueller (2002) Nature Struct. Biol. Vol. 9(5) Pp 320-322.

  • Sivaraman J, Sauve V, Matte A, Cygler M. Crystal structure of Escherichia coli glucose-1-phosphate thymidylyltransferase (RffH) complexed with dTTP and Mg2+. J Biol Chem.(2002)Nov 15;277(46):44214-9

* Corresponding author(s)

 
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Last modified on Jul 2007 by Department of Biological Sciences