Profile: Joydip Das
Associate Professor of Medicinal Chemistry
542 D Science and Research Building 2
Houston, TX 77204-5037
M.Sc. in Organic Chemistry, University of Burdwan, India
B.Sc. in Chemistry (with Honors), University of Calcutta, India
Postdoctoral: Medical University of South Carolina, Massachusetts Institute of Technology and Massachusetts General Hospital.
Actions of alcohol on presynaptic proteins:
Effect of ethanol on presynaptic function is not well studied. We are interested in the actions of alcohol on the proteins involved in the presynaptic SNARE complex that regulates synaptic vesicle fusion and neurotransmitter release. Munc 13-1 is one of such presynaptic active zone-protein. It is also implicated in modulating short-term presynaptic plasticity. We have located the alcohol binding site of Munc13-1 near the Glu-582 at its C1 domain by photolabeling and mass spectrometry. Functional characterization of the alcohol binding residues is under investigation.
Development of subtype specific PKC activators/inhibitors:
Protein Kinase C (PKC) is a serine threonine kinase that plays a central role in signal transduction, regulating divergent cellular functions. Aberrations in PKC signaling have been implicated in the development of multiple human diseases including several types of cancer, metabolic and cardiovascular complications of diabetes, central nervous system dysfunctions, neuronal degeneration and cardiovascular disorders and alcoholism Our ongoing research aims at developing subtype specific activators/inhibitors leading to therapeutics. We are developing molecules based on simple chemical scaffold such as, curcumin and resveratrol and testing their effects on subtype-specific PKC activities.
We use protein biochemistry, X-ray crystallography, mass spectrometry, cell culture, organic synthesis and molecular docking techniques for our studies.
- PCOL 7297 Drug design and discovery
- PHAR 5302 Medicinal Chemistry I
- PHAR 5203 Medicinal Chemistry II
- PHPS 3101 Chemical functional group analysis
- PHPS 4301 Medicinal Chemistry I
J. Das, S. Xu, S. Pany, A. Guillory and G.W. Roman. The presynaptic Munc13-1 binds alcohol and modulates alcohol self-administration in Drosophila, J. Neurochem. 2013 May 20. doi: 10.1111/jnc.12315. [Epub ahead of print]
J. Das. Protein Kinase C: the drug target one must see, Med. Chem. 2, e103. Doi: 10.4172/2161-0444.1000e103.
G.M. Rahman, S. Shanker, N.E. Lewin, B.V.V. Prasad, P.M. Blumberg and J. Das. Identification of the Activator Binding Residues in the Second Cysteine-Rich Regulatory Domain of Protein Kinase C Theta (PKCθ), Biochem. J. 2013 Apr 1;451(1):33-44. doi: 10.1042/BJ20121307.
S. Pany, A. Majhi and J. Das. PKC activation by resveratrol analog with unsaturated aliphatic chain. PLOS ONE, 2012;7(12):e52888. doi: 10.1371/journal.pone.0052888
S. Shanmugasundararaj*, J. Das*, W.S. Sandberg, X. Zhou, D. Wang, R.O. Messing, K. S. Bruzik, T. Stehle and K.W. Miller. Structural and functional characterization of an anesthetic binding site in the second cysteine rich domain of protein kinase C delta, Biophys. J., 2012 Dec 5;103(11):2331-40. doi: 10.1016/j.bpj.2012.10.034. *joint 1st authors
J. Das, S. Pany and A. Majhi, Chemical modification of resveratrol for improved PKC alpha activity Bioorg. Med. Chem. 19, 5321-5333 (2011)
J. Das, S. Pany, S. Panchal, A. Majhi and G.M. Rahman. Binding of isoxazole and pyrazole derivatives of curcumin with the activator binding domain of novel protein kinase C. Bioorg. Med. Chem. 2011 Nov 1;19(21):6196-202. doi: 10.1016/j.bmc.2011.09.011.
S.C. Gupta, R. Kannapan, J. Hye Kim, G. M. Rahman, S.K. Francis, R. Raveendran, M.S. Nair, J. Das and B.B. Aggarwal. Bharangin, a Diterpenoid Quinonemethide, Abolishes Constitutive and Inducible NF-kB Activation by Modifying p65 on Cysteine 38 residue and Inhibiting IkBalpha Kinase Activation, Leading to Suppression of NF-kB-Regulated Gene expression and Sensitization of Tumor Cells to Chemotherapeutic Agents., Mol. Pharmacol. 2011 Nov;80(5):769-81. doi: 10.1124/mol.111.073122.
J. Das. Aliphatic diazirines as probes for proteins: recent developments. Chem. Rev. 2011 Aug 10;111(8):4405-17. doi: 10.1021/cr1002722.
R. Howard, P. Slesinger, D. Davies, J. Das, R. Harris and J. Trudell. Alcohol-binding sites in distinct brain proteins: the quest for atomic level resolution. Alcohol Clin Exp Res. 2011 Sep;35(9):1561-73. doi: 10.1111/j.1530-0277.2011.01502.x.
Majhi, G.M. Rahman, S. Panchal and J. Das. Binding of curcumin and its long chain derivatives to the activator binding domain of novel Protein Kinase C. Bioorg Med Chem. 2010 Feb 15;18(4):1591-8. doi: 10.1016/j.bmc.2009.12.075.
J. Das, S. Pany, G. M. Rahman and S. J. Slater. PKC epsilon has an alcohol binding site in its second cysteine rich regulatory domain, Bioorg Med Chem. Biochem J. 2009 Jul 15;421(3):405-13. doi: 10.1042/BJ20082271. Erratum in: Biochem J. 2009 Nov 1;423(3):442.
J. Das. Photoincorporation of azioctanol to the C1B domain of PKC delta is buffer dependent. J Photochem Photobiol B. 2009 Jun 3;95(3):185-8. doi: 10.1016/j.jphotobiol.2009.03.004.
J. Das, X. Zhou and K. W. Miller. Identification of an alcohol binding site in the first cysteine-rich domain of Protein Kinase C delta. Protein Sci. 2006 Sep;15(9):2107-19.
J. Das, G. H. Addona, W. S. Sandberg, S. S. Husain, T. Stehle and K. W. Miller (2004) Identification of a general anesthetic binding site in the diacylglycerol–binding domain of Protein Kinase C delta, J. Biol. Chem., 279, 37964-37972.
J. Das, M. Kono, J-x. Ma, D.D. Oprian and R.K. Crouch (2004) C9 methyl group of retinal modulates the absorption and transducin activation properties in cone pigments, Biochemistry, 43, 5532-5538.
J. Ma, S. Znoiko, K.L. Othersen, J.C. Ryan, J. Das , T. Isayama, M. Kono, D.D. Oprian, D.W. Corson, M.C. Cornwall, D.A. Cameron, F.I. Harosi, C.L. Makino, R.K. Crouch (2001) A visual pigment expressed in both rod and cone photoreceptors. Neuron, 32, 451-461.
J. Ma, M. Kono, L. Xu, J. Das, J. C. Ryan, E. S. Hazard III, D. D. Oprian and R. K. Crouch (2001) Cloning, expression and spectral analysis of the Salamander UV cone visual pigment, Vis. Neuroscience, 18,393-399.
J. Das, R. K. Crouch and P. L. Chong (2000) Fluorescence properties of pyrylretinol, Photochem. Photobiol., 72, 415-422.
H. Stecher, O Prezhdo, J. Das, R. K. Crouch and K. Palczewski (1999)Isomerization of all-trans-9- and 13-desmethylretinol by retinal pigment epithelial cells, Biochemistry, 38, 13542-13550.
J. Das, R. K. Crouch, R. Govindjee and T.G. Ebrey (1999) Studies on the Pyryl retinal analogues of bacteriorhodopsin, Photochem. Photobiol., 70, 949-956.
S. Xu, S. Pany, V. Shah, J. Das and G. Roman, UNC-13, a presynaptic ethanol binding protein in regulates alcohol-related behavior in drosophila, Alcohol. Clin. Ex. Res., 37S, 2013, 71A
S. Xu, S. Pany, J. Das and G. Roman. Reducing UNC-13, a presynaptic ethanol binding protein in drosophila melanogaster increases ethanol self-administration, Alcohol. Clin. Ex. Res., 36S, 2012, 258A
J. Das and S. Pany. Binding of alcohol to the C1 domain of PKC epsilon, Alcohol. Clin. Ex. Res., 36S, 2012, 15A
G.M. Rahman, S. Sanker, N. Lewin, B.V.V. Prasad, P.M. Blumberg and J. Das. Identification of the activator binding residues in protein kinase C theta C1B domain FASEB J., 2012 26:749.2
G.M. Rahman, S. Shanker, N. Lewin, B.V.V. Prasad, P.M. Blumberg and J. Das, Comparison of the activator binding residues of PKC, 39th MALTO abstract book, 2012, p24
S. Pany, A. Majhi and J. Das. Selectivity of curcumin and its analogs for conventional PKCs, 39th MALTO abstract book, 2012, p49.
J. Das, S. Pany, S. Xu, V. Shah and G. Roman. Presynaptic Munc13.1 is a potential target of alcohol action, in From Innovation in Nucleic acid research to regulation of biological processes, Abstract book, 2011, p185
J. Das and S. Pany. Interactions of presynaptic munc13.1 with alcohols, Alcohol. Clin. Ex. Res., 35S, 2011, 256A
G.M. Rahman and J. Das. Identification of activator binding residues in PKCthetaC1B domain: the effect of mutation in activator binding, 38th MALTO abstract book, 2011, p41
S. Pany, A. Majhi and J. Das. Synthesis and evaluation of resveratrol analogues as PKC alpha modulators, 38th MALTO abstract book, p 52
Pany, S. and J. Das. Presynaptic munc 13.1, a molecular target of alcohol? Program No. 473.14/JJ10. 2010 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2010. Online.
Z. Trivedi, G.M. Rahman and J. Das. Effects of mutations in the C1B subdomain of PKC gamma on activator binding, University of Houston Research Day Poster session, 2010.
S. Panchal, A. Majhi, V. Tam and J. Das, Synthesis of Poly-Phenolic Derivatives and Evaluation for Anti-Bacterial and Anti-Fungal Activity, University of Houston Research Day Poster session, 2009.
J. Das and G. M. Rahman, Development of alcohol antagonists based on Protein Kinase C epsilon, Alcohol. Clin. Exp. Res., 33(6), 2009, suppl. Issue, p17A
A. Majhi, S. Panchal, G.M. Rahman and J. Das., Interaction protein Kinase C and Curcumin and its derivatives, Thirty-Sixth Annual MALTO, Memphis, May 17-19, 2009
A. Guillory, S. Pany and J. Das, Alcohol binding site(s) in the C1 domain of MUNC 13.1, Thirty-Sixth Annual MALTO, Memphis, May 17-19, 2009
G.M. Rahman and J. Das., Virtual molecular docking study of DAG and phorbol ester-like compounds to explore the differential binding affinity of C1A and C1B subdomains of Novel PKCs, Thirty-Sixth Annual MALTO, Memphis, May 17-19, 2009
A. Guillory, S. Pany and J. Das, Alcohol binding site(s) in the C1 domain of PKC epsilon and MUNC 13.1, Behavior, Biology, Chemistry: Translational Research in Addiction, San Antonio, TX March 21-22, 2009 (Travel Award to A. Guillory).
J. Das, Role of histidine and tyrosine residues in the alcohol binding in Protein Kinase C Epsilon, Alcohol. Clin. Exp. Res., 32(6), 2008, suppl. Issue, p161A.
J. Das, S. Shunmugasundararaj, T. Stehle, and K. W. Miller. Crystal structure of an alcohol complexed with the cysteine-rich domain of Protein Kinase C delta. Alcohol. Clin. Exp. Res., 2007, 31(6), suppl. Issue, p202A
J. Das. Investigation on the alcohol binding site(s) in the cysteine-rich domain of Protein Kinase C epsilon. Alcohol. Clin. Exp. Res., 2007, 31(6), suppl. Issue, p195A.
J. Das and K. W. Miller. In the C1 domain of Protein Kinase C delta both C1A and C1B contain an alcohol binding domain. Biophys. J. 2006; 90(1):40a.
J. Das and K. W. Miller. Identification of an alcohol binding site in the first cysteine rich domain of protein kinase C delta by photolabeling and mass spectrometry. Biophys. J. 2005; 88(1):45a
Invited Lectures and Seminars
Invited Talk at the University of Wisconsin, Eau Claire, Oct. 7, 2011, titled “Alcohol Binding Sites in Brain Proteins.
Jadavpur University, Calcutta, India, January 2008.
The University of Texas at El Paso, Texas, November 2007
Indiana Centers for Applied Protein Sciences, Indianapolis, Indiana, October 2005
Curagen Corporation, Branford, Connecticut, March 2004
- American Chemical Society
- Protein Society
- Research Society on Alcoholism
- Biophysical Society
- American Society for Photobiology