Title

Authors

Affiliation

¹Computational Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati-781039, Assam, India; ²Biotech Hub, Centre for the Environment, Indian Institute of Technology Guwahati, Guwahati-781039, Assam, India.

Email

ubora@iitg.ernet.in; *Corresponding author

Article Type

Hypothesis

Date

Received October 04, 2012; Accepted October 05, 2012; Published October 13, 2012

Stat3 is a mammalian transcription factor which regulates various genes involved in cell growth, proliferation, cell survival and other biological processes. Its constitutive activation promotes dysregulated growth, survival and immune responses which contribute to tumor progression and carcinogenesis. Inhibition of Stat3 dimerization which prevents its binding to DNA is a rational strategy that could be translated to potential therapeutic applications. The present computational study provides insights into the inhibition of Stat3 dimerization by curcumin natural derivatives and its conjugates with amino acids. The involvement of residues like LYS-591, ARG-609, SER-611, GLU-612, SER-613, SER-636 and VAL-637 seems to play an important role in binding of curcumin natural derivatives and its amino acids conjugates with Src Homology (SH2) domain of Stat3 monomer. Demethoxycurcumin followed by hexahydrocurcuminol were predicted to be the most potent inhibitors amongst all the curcumin natural derivatives and known inhibitors (FLLL32, Sta21 and Stattic). Curcumin-proline conjugate (1,7-Bis(4-O-L-prolinoyl-3-methoxyphenyl)-1,4,6-heptatriene-5-ol-3-one) was predicted to be the most potent inhibitor of Stat3 dimerization amongst the curcumin-amino acid conjugates and known peptide based inhibitor (Phpr-pTYR-LEU-cis-3,4-methanoPRO-GLN-NHBn).

Keywords

Curcumin natural derivatives, Curcumin–amino acid conjugates, Stat3 dimerization, Src Homology (SH2) domain, Molecular docking.

Citation

Kumar & Bora, Bioinformation 8(20): 988-993 (2012)
 

Edited by

P Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.