Interaction of Virstatin with Human Serum Albumin: Spectroscopic Analysis and Molecular ModelingReport as inadecuate




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Virstatin is a small molecule that inhibits Vibrio cholerae virulence regulation, the causative agent for cholera. Here we report the interaction of virstatin with human serum albumin HSA using various biophysical methods. The drug binding was monitored using different isomeric forms of HSA N form ∼pH 7.2, B form ∼pH 9.0 and F form ∼pH 3.5 by absorption and fluorescence spectroscopy. There is a considerable quenching of the intrinsic fluorescence of HSA on binding the drug. The distance r between donor Trp214 in HSA and acceptor virstatin, obtained from Forster-type fluorescence resonance energy transfer FRET, was found to be 3.05 nm. The ITC data revealed that the binding was an enthalpy-driven process and the binding constants Ka for N and B isomers were found to be 6.09×105 M−1 and 4.47×105 M−1, respectively. The conformational changes of HSA due to the interaction with the drug were investigated from circular dichroism CD and Fourier Transform Infrared FTIR spectroscopy. For 1∶1 molar ratio of the protein and the drug the far-UV CD spectra showed an increase in α- helicity for all the conformers of HSA, and the protein is stabilized against urea and thermal unfolding. Molecular docking studies revealed possible residues involved in the protein-drug interaction and indicated that virstatin binds to Site I subdomain IIA, also known as the warfarin binding site.



Author: Tanaya Chatterjee , Aritrika Pal, Sucharita Dey, Barun K. Chatterjee, Pinak Chakrabarti

Source: http://plos.srce.hr/



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