Research Groups
Mammalian Biology: Structural and Computational Biology
Research Interests and Description
Research Interests
Protein structure, function and crystallography.
Description of Research
Description of Research
The well established Group on Structural and Computational Biology at ICGEB, New Delhi has made many pivotal contributions in highlighting structural principles that govern biology. The Group has made a niche in structural biology of crucial malaria parasite proteins, and we have additional expertise in membrane protein structure determination and NMR. The combined expertise in the Group grants a position to link with new discoveries made in terms of molecular targets against infectious diseases. Our results so far have opened avenues for (a) investigating new facets of malaria parasite biology, and (b) design of inhibitors against critical malaria parasite developmental stages.
Protein crystallographic studies of malaria parasite proteins
The laboratory takes a multi-disciplinary approach towards understanding malaria parasite proteins. We aim to highlight the principles that govern biological function of key parasite proteins. Towards this end, we rely extensively on bioinformatics, biochemistry, cell biology, molecular biology, parasitology and protein crystallography. Using multi-disciplinary approaches, we have been successful at elucidating structure-function relationships for several crucial parasite proteins, and we hope that these analyses will guide therapeutic developments against malaria. Complex life cycle of the malaria parasite necessitates an elaborate protein repertoire which is tightly regulated. This requirement highlights two important enzymatic families whose main function is in protein translation, its fidelity and proof reading: (1) aminoacyl-tRNA synthetases, and (2) D-amino acid tRNA deacylase. Structural studies on both these systems are likely to throw light on their mechanism of action, and may help in rational drug design against these. Amongst the many processes fundamentally important to the parasite, one involves packaging DNA into nucleosomes and chromatin. Several specialized parasite proteins perform DNA compaction and we are working on two such proteins called Nucleosome Assembly Proteins (Pf-NAPz). These two proteins interact with other essential parasite proteins like histones to assemble and disassemble nucleosomes. Further, P. falciparum NAPz are important for cellular activities like DNA repair, DNA recombination and transcription. We have identified a role for PfNAPz in histone transport and nucleocytoplasmic shuttling. Therefore, we propose to investigate, in considerable detail, biological features of the two P. falciparum NAPz in order to further our understanding of the DNA packing process within the parasite.
Recent Publications
Jackson, K.E., Habib, S., Frugier, M., Hoen, R., Khan, S., Pham, J.S., Pouplana, L.R., Royo, M., Santos, M.A., Sharma, A., Ralph, S.A. 2011. Protein translation in Plasmodium parasites. Trends Parasitol. 2011 Jul 6. [Epub ahead of print] PubMed link
Sharma, A., Sharma, A. 2011. Fatty acid induced remodeling within the Human liver fatty acid binding protein. J Biol Chem. 2011 Jul 8. [Epub ahead of print] PubMed link
Bhatt, T.K., Yogavel, M., Wydau, S., Berwal, R., Sharma, A. 2010. Ligand-bound Structures Provide Atomic Snapshots for the Catalytic Mechanism of D-Amino Acid Deacylase. J Biol Chem 285, 5917-5930 PubMed link
Camarda, G., Bertuccini, L., Singh, S.K., Salzano, A.M., Lanfrancotti, A., Olivieri, A., Scaloni, A., Sharma, A., Alano, P. 2010. Regulated oligomerisation and molecular interactions of the early gametocyte protein Pfg27 in Plasmodium falciparum sexual differentiation. Int J Parasitol. 40, 663-673 PubMed link
Gill, J., Kumar, A., Yogavel, M., Belrhali, H., Jain, S.K., Rug, M., Brown, M., Maier, A.G., Sharma, A. 2010. Structure, localization and histone binding properties of nuclear-associated nucleosome assembly protein from Plasmodium falciparum. Malar J. 9, 90 PubMed link
Yogavel, M., Nithya, N., Suzuki, A., Sugiyama, Y., Yamane, T., Velmurugan, D., Sharma, A. 2010. Structural analysis of actinidin and a comparison of cadmium and sulfur anomalous signals from actinidin crystals measured using in-house copper- and chromium-anode X-ray sources. Acta Crystallogr D Biol Crystallogr. 66, 1323-1333. PubMed link
