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Exploring the binding dynamics of etoricoxib with human hemoglobin: A spectroscopic, calorimetric, and molecular modeling approach
Published in Taylor and Francis Ltd.
PMID: 30080442
Volume: 37
Issue: 11
Pages: 3018 - 3028
Etoricoxib, widely used for the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and related conditions has ample affinity to bind with globular proteins. Here, the molecular interaction between purified human hemoglobin (HHb), a major heme protein and etoricoxib, a cyclooxygenase-2 inhibitor was studied by various spectroscopic, calorimetric, and molecular modeling techniques. The binding affected hypochromic changes in the Soret band of hemoglobin (Hb) and induced remarkable quenching of the intrinsic fluorescence property of protein molecules. Synchronous fluorescence studies revealed alterations in tryptophan (Trp) and tyrosine (Tyr) microenvironments of HHb molecule in presence of etoricoxib. Flouremetric and isothermal titration calorimetric studies suggested two binding sites in HHb for etoricoxib at three different temperatures (298.15, 303.15, and 310.15 K). Negative values of Gibbs energy change (ΔG0) and enthalpy change (ΔH0) strongly suggest that it is spontaneous and exothermic reaction, mainly stabilized by hydrogen bonding as evidenced by sucrose binding assay. These findings support our in silico molecular docking study, which specified the binding site and the non-covalent interactions involved in the association. Moreover, the interaction impacts on structural integrity and functional aspects of HHb as confirmed by decreased α helicity, increased free iron release, increased rate of co-oxidation, and decreased rate of esterase activity. Overall, these studies conclude that etoricoxib leads to a remarkable alteration in the conformational aspects of binding to HHb. Communicated by Ramaswamy H. Sarma. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.
About the journal
JournalData powered by TypesetJournal of Biomolecular Structure and Dynamics
PublisherData powered by TypesetTaylor and Francis Ltd.
Open AccessNo