Chittaranjan Das

PULSe Contributor - not currently hosting students for laboratory rotations or recruiting students in the laboratory

Current Research Interests:

Currently, we are investigating the normal function of the neuronal DUB ubiquitin C-terminal hydrolase L1 (UCHL1)- a PD-associated, neuron-specific protein of unknown physiological function. Our efforts in this direction are aimed at developing cell-permeable small molecule inhibitors of UCHL1 that can be used to probe its function (both normal and disease-associated), determining its binding partners by affinity based purification from whole-cell extracts, and defining the molecular basis of how a naturally occurring variant of this enzyme- in which Ser at the position 18 is substituted by Tyr (called the S18Y polymorph)- provides protection from Parkinson's disease (PD). In addition to UCHL1, we are also conducting structural and mechanistic investigations of other related enzymes thought to be involved in fundamental biochemical processes such as DNA repair, histone modification, and endocytosis of plasma membrane proteins.

Selected Publications:

Das,C., Hoang,Q.Q., Kreinbring,C.A., Luchansky, S.J., Meray,R.K., Ray,S.S., Lansbury,P.T., Ringe,D., Petsko,G.A., "Structural basis of conformational plasticity of the Parkinson's disease- associated ubiquitin hydrolase UCH-L1", Proceedings of the National Academy of Sciences USA 2006, 103, 4675-4680.

Kornilova,A.Y., Bihel,F., Das,C., Wolfe,M.S., "The initial substrate-binding site of gamma-secretase is located on presenilin near the active site", Proceedings of the National Academy of Sciences USA 2005, 102, 3230-3235.

Bihel,F., Das,C., Bowman,M.J., Wolfe,M.S., "Discovery of a Subnanomolar helical D-tridecapeptide inhibitor of gamma-secretase", J Med Chem. 2004, 47, 3931-3933.

Esler,W.P., Das,C., Wolfe,M.S., "Probing pockets S2-S4' of the gamma-secretase active site with (hydroxyethyl)urea peptidomimetics", Bioorg Med Chem Lett. 2004, 14, 1935-1938.