Acetaminophen interacts with human hemoglobin: optical, physical and molecular modeling studies.
Acetaminophen, a widely used analgesic and antipyretic drug has ample affinity to bind globular proteins. Here, we have illustrated a substantive study pertaining to the interaction of acetaminophen with human hemoglobin (HHb). Different spectroscopic (absorption, fluorescence, and circular dichroism (CD) spectroscopy), calorimetric, and molecular docking techniques have been employed in this study. Acetaminophen-induced graded alterations in absorbance and fluorescence of HHb confirm their interaction. Analysis of fluorescence quenching at different temperature and data obtained from isothermal titration calorimetry indicate that the interaction is static and the HHb has one binding site for the drug. The negative values of Gibbs energy change (ΔG0) and enthalpy changes (ΔH0) and positive value of entropy change (ΔS0) strongly suggest that it is entropy-driven spontaneous and exothermic reaction. The reaction involves hydrophobic pocket of the protein which is further stabilized by hydrogen bonding as evidenced from ANS and sucrose binding studies. These findings were also supported by molecular docking simulation study using AutoDock 4.2. The interaction influences structural integrity as well as functional properties of HHb as evidenced by CD spectroscopy, increased rate of co-oxidation and decreased esterase activity of HHb. So, from these findings, we may conclude that acetaminophen interacts with HHb through hydrophobic and hydrogen bonding, and the interaction perturbs the structural and functional properties of HHb.
a Department of Physiology , University Colleges of Science and Technology, University of Calcutta , 92, A.P.C. Road, Kolkata 700 009 , India.
Paromita
P
Seal
a Department of Physiology , University Colleges of Science and Technology, University of Calcutta , 92, A.P.C. Road, Kolkata 700 009 , India.
Jyotirmoy
J
Sikdar
a Department of Physiology , University Colleges of Science and Technology, University of Calcutta , 92, A.P.C. Road, Kolkata 700 009 , India.
Amartya
A
Roy
a Department of Physiology , University Colleges of Science and Technology, University of Calcutta , 92, A.P.C. Road, Kolkata 700 009 , India.
Rajen
R
Haldar
D000082:Acetaminophen / Q000737:chemistry* / Q000378:metabolism; D000328:Adult; D001665:Binding Sites; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D013057:Spectrum Analysis / Q000379:methods; D013816:Thermodynamics; D055815:Young Adult
D006454:Hemoglobins; D000082:Acetaminophen
acetaminophen; human hemoglobin; isothermal titration calorimetry; molecular modeling; spectroscopy