Curcumin recognizes a unique binding site of tubulin.
Summary of "Curcumin recognizes a unique binding site of tubulin."
Although curcumin is known for its anticarcinogenic properties, the exact mechanism of its action or the identity of the target receptor is not completely understood. Studies on a series of curcumin analogues, synthesized to investigate their tubulin binding affinities and tubulin self-assembly inhibition, showed that: (i) curcumin acts as a bifunctional ligand, (ii) analogues with substitution at the diketone and acetylation of the terminal phenolic groups of curcumin are less effective, (iii) a benzylidiene derivative, compound 7, is more effective than curcumin in inhibiting tubulin self-assembly. Cell-based studies also showed compound 7 to be more effective than curcumin. Using fluorescence spectroscopy we show that curcumin binds tubulin 32 Å away from the colchicine-binding site. Docking studies also suggests that the curcumin-binding site to be close to the vinblastine-binding site. Structure-activity studies suggest that the tridented nature of compound 7 is responsible for its higher affinity for tubulin compared to curcumin.
Affiliation
Department of Biochemistry, Bose Institute , Centenary Campus, P-1/12 CIT Scheme VIIM, Kolkata 700054, India.
Journal Details
This article was published in the following journal.
Name: Journal of medicinal chemistry
ISSN: 1520-4804
Pages: 6183-96
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21830815
- DOI: http://dx.doi.org/10.1021/jm2004046
Medical and Biotech [MESH] Definitions
Ribosome Subunits, Small
The small ribonucleoprotein component of RIBOSOMES. It contains the MESSENGER RNA binding site and two TRANSFER RNA binding sites - one for the incoming AMINO ACYL TRNA (A site) and the other (P site) for the peptidyl tRNA carrying the elongating peptide chain.
Tubulin Modulators
Agents that interact with TUBULIN to inhibit or promote polymerization of MICROTUBULES.
Curcumin
A yellow-orange dye obtained from tumeric, the powdered root of CURCUMA longa. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes.
Allosteric Site
A site on an enzyme which upon binding of a modulator, causes the enzyme to undergo a conformational change that may alter its catalytic or binding properties.
Microtubules
Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS.
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