Abstract
BackgroundHuman serum albumin (HSA) is the most abundant protein in blood plasma, having high affinity binding sites for several endogenous and exogenous compounds. Trimethoxy flavone (TMF) is a naturally occurring flavone isolated from Andrographis viscosula and used in the treatment of dyspepsia, influenza, malaria, respiratory functions and as an astringent and antidote for poisonous stings of some insects.Methodology/Principal FindingsThe main aim of the experiment was to examine the interaction between TMF and HSA at physiological conditions. Upon addition of TMF to HSA, the fluorescence emission was quenched and the binding constant of TMF with HSA was found to be KTMF = 1.0±0.01×103 M−1, which corresponds to −5.4 kcal M−1 of free energy. Micro-TOF Q mass spectrometry results showed a mass increase of from 66,513 Da (free HSA) to 66,823 Da (HAS +Drug), indicating the strong binding of TMF with HSA resulting in decrease of fluorescence. The HSA conformation was altered upon binding of TMF to HSA with decrease in α-helix and an increase in β-sheets and random coils suggesting partial unfolding of protein secondary structure. Molecular docking experiments found that TMF binds strongly with HSA at IIIA domain of hydrophobic pocket with hydrogen bond and hydrophobic interactions. Among which two hydrogen bonds are formed between O (19) of TMF to Arg 410, Tyr 411 and another one from O (7) of TMF to Asn 391, with bond distance of 2.1 Å, 3.6 Å and 2.6 Å, respectively.Conclusions/SignificanceIn view of the evidence presented, it is imperative to assign a greater role of HSA's as a carrier molecule for many drugs to understand the interactions of HSA with TMF will be pivotal in the design of new TMF-inspired drugs.
Highlights
Flavonoids are naturally occurring polyphenolic compounds used as food supplements which has anti-allergic, anti-inflammatory, anti-microbial and anti-cancer activity
The emission fluorescence of Human serum albumin (HSA) comes from tryptophan, tyrosine, and phenylalanine
Different concentrations of Trimethoxy flavone (TMF) were used to study the interaction with HSA
Summary
Flavonoids are naturally occurring polyphenolic compounds used as food supplements which has anti-allergic, anti-inflammatory, anti-microbial and anti-cancer activity. The interactions of TMF with HSA was investigated by using fluorescence emission, circular dichroism (CD), micro-TOF Q mass spectrometry and molecular docking studies. With increasing concentrations of TMF (0.005 to 0.08 mM) and a fixed concentration of HSA (0.025 mM), the maximum fluorescence (362 nm) of HSA was quenched upon binding of TMF
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