Dr. Ruchi Anand

    Assistant Professor

    Department of Chemistry

    Indian Institute of Technology Bombay

    Powai, Mumbai 400076

    Ph:   022-2576 7165

    Fax:  022-2576 7152

    Email: ruchi[at]chem.iitb.ac.in

    Group Webpage

 

Academic Background

Ph.D.(Chemistry) (Cornell University, 2004)

M.Sc.(Chemistry) (Indian Institute of Technology, Kanpur)

B.Sc. (Chemistry) (Delhi University)

 

Research Interests

 

The research focus in our group is on Structural Biochemistry, we employ a combination of biochemical and crystallographic techniques to understand, mechanism of catalysis, structure-function relationship, protein-protein interactions of various enzymes and protein-DNA complexes. The three-dimensional structure enables us to visualize protein structures at the atomic level and enhances our understanding of protein function, how they undergo conformational changes, and how they perform catalysis. Armed with this information we can design novel drugs that target a particular protein, or rationally engineer an enzyme to find cures for specific diseases. In order to further characterize them we develop specialized assays for protein of interest.


Mechanism of Regulation of Mammalain Sterile 20 family of Kinases

 

Primarily we work on proteins and transcription factors involved in cell signaling and apoptosis pathways. One of our main focus is to study Ste20 family of protein kinases. Kinases, the biological backbone of the signaling pathway are investigated using a combination of protein crystallography and chemical screening assay systems. The goal is to use structure based drug design as a tool to develop potential drug targets. The Ste20 family member of kinases are serine/threonine kinases and many of them are involved in aspects of regulation of the ubiquitously well known mitogen activated cell signaling pathway. Misregulation of this family of kinases can lead to diseases like breast cancer, cardiomyopathy and other neurodegenerative disorders. .

One of the kinases we are investigating is MST kinase. It phosphorlates histone H2B in the nucleus and initiates chromatin unwinding a hallmark associated with apoptosis. Whereas, in the cytoplasm it activates the FoxO class of DNA binding transcription factor. The FoxO, transcription factor is strategically placed and activation of FoxO is associated with diseases like diabetes and neurological disorders. We are probing their mechanism of regulation and are also trying to understand the structural basis of differential substrate specificity. We are adopting a combination of biochemical and structural biology approaches to answer our questions.

Inhibitor Screening


Several protein kinases are important therapeutics targets for diseases. We are employing virtual (computational) and chemical screening approaches to charter the chemical space in order to find competent small molecule inhibitors as potential drug targets against both serine/threonine and tyrosine kinases. We are using Structural biochemistry as a tool to fine-tune the inhibitors for efficient drug design. The information available from a X-ray structure helps in intelligent development of inhibitor design.


Protein Substrate Channeling


A common question posed when studying enzyme systems is how do unstable intermediates channel from one enzyme to another without getting degraded? Many of these enzyme systems either mediate these intermediates by forming multi-protein complexes, via protein-protein interactions. In certain cases the active sites are fused and internal channels are pre-formed to facilitate the transfer. We are interested in probing the mechanism of channeling in certain enzymes in the purine de nova biosynthetic pathway. This biosynthetic pathway is essential for the synthesis of purine bases, precursors to DNA. Since it is an essential pathway for cell survival differences in the pathway among humans and pathogenic bacterial can be exploited for drug development. We are using a combination of biochemical analysis in conjunction with X-ray crystallography to understand the mechanism of catalysis and channeling.

 

Representative Publications

  • R Anand, N. Pagano, J. Maksimoska, E. Wong, S. L. Diamond, E. Meggers, R. Marmorstein Development of a Potent and Specific Organoruthenium Mammalian Sterile 20 Kinase Inhibitor, 2008 Journal of Medicinal Chemistry (under revision)

  • M. Brent, R. Anand, R. Marmorstein, Structural Basis for DNA Recognition by FoxO1 and its Regulation by Post-Translational Modification, 2008 Structure (in press)

  • R. Anand, A. Kim, M. Brent, R. Marmorstein, Biochemical Analysis of MST1 Kinase: Elucidation of a C-Terminal Regulatory Region, Biochemistry, 42,2008 (25); 6719-6726

  • R Anand , R Marmorstein Structure and mechanism of lysine-specific demethylase enzymes.J Biol Chem. 2007 ,282(49):35425-9

  • M.Morar, R. Anand, J. Stubbe, S.E. Ealick, Complexed structures of formylglycinamide ribonucleotide amidotransferase from Thermotoga maritima describe a novel ATP binding protein superfamily Biochemistry 2006 14880.

  • R. Anand, A. A Hoskins, E. M. Bennett, M.D.Sintchak, J. Stubbe, S.E. Ealick, A model for the Bacillus subtilis formylglycinamide ribonucleotide amidotransferase multiprotein complex. Biochemistry 2004 10343.

  • R. Anand, A.A Hoskins, J. Stubbe, S.E. Ealick, Domain organization of Salmonella typhimurium formylglycinamide ribonucleotide amidotransferase revealed by X-ray crystallography Biochemistry 2004 10328.

  • A.A Hoskins, R. Anand, S.E. Ealick, J. Stubbe, The formylglycinamide ribonucleotide amidotransferase complex from Bacillus subtilis: metabolite mediated complex formation Biochemistry 2004 10320.

  • R. Anand, P.A. Kaminski, S.E. Ealick, Structure of Purine 2'- Deoxyribosyltransferase, Substrate Complexes and the Ribosylated Intermediate at 1.75Å Resolution Biochemistry. 2004, 2384.

  • E.M. Bennett, R. Anand, P.W. Allan, A.E. Hassan, J.S. Hong, D.N. Levasseur, D.T. McPherson, W.B. Parker, J.A Secrist III, E.J. Sorcher, T.M. Townes, W.R. Waud, S.E. Ealick, Designer Gene Therapy Using an Escherichia coli Purine Nucloside Phosphorylase/Prodrug System Chemistry & Biology 2003, 10, 1173.

  • R. Anand, P.C. Dorrestein, C. Kinsland, T. Begley, S.E. Ealick, "Structure of Oxalate Decarboxylase from Bacillus Subtilis at 1.75Å Resolution" Biochemistry 2002, 7659.