Spectroscopic, calorimetric and in silico insight into the molecular interactions of Memantine with human transferrin: Implications of Alzheimer's drugs

Human transferrin (Tf) is an iron-binding blood plasma glycoprotein that controls free iron in biological fluids. Tf is a liver-produced protein that binds iron very tightly but reversibly and is the most significant iron pool. Memantine is an orally administrative N-methyl-d-aspartate glutamate rec...

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Published inInternational journal of biological macromolecules Vol. 190; pp. 660 - 666
Main Authors Shamsi, Anas, Shahwan, Moyad, Alhumaydhi, Fahad A., Alwashmi, Ameen S.S., Aljasir, Mohammad Abdullah, Alsagaby, Suliman A., Al Abdulmonem, Waleed, Hassan, Md. Imtaiyaz, Islam, Asimul
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 01.11.2021
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Summary:Human transferrin (Tf) is an iron-binding blood plasma glycoprotein that controls free iron in biological fluids. Tf is a liver-produced protein that binds iron very tightly but reversibly and is the most significant iron pool. Memantine is an orally administrative N-methyl-d-aspartate glutamate receptor antagonist used to slow the progression of moderate-to-severe Alzheimer's disease (AD) and dementia. Here, we have investigated the molecular interactions of Memantine with Tf using molecular docking, dynamics simulation and in vitro binding studies. Molecular docking study revealed many close interactions of Memantine towards Tf with an appreciable binding affinity. The docking results were further validated by molecular dynamics (MD) simulation studies, followed by essential dynamics and free energy landscapes analyses. Memantine shows a good binding affinity to the Tf with a binding constant (K) of 105 M-1. Isothermal titration calorimetry (ITC) also advocated the spontaneous binding of memantine to Tf. The study proposed that the Memantine in complex with Tf is stable in the simulated trajectory with minimal structural changes. The study suggested that the Tf-Memantine interactions can be further explored in AD therapy after critical exploration. •Homeostasis of metal ions in the brain is vital for normal physiological functions.•Transferrin is a key player in iron homeostasis and fourth richest plasma protein.•Memantine shows a good binding affinity to the Tf with a binding constant (K) of 105 M-1.•Isothermal titration calorimetry (ITC) also advocated spontaneous binding.•Tf-memantine complex is stable in simulated trajectory with minimal structural changes.
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ISSN:0141-8130
1879-0003
DOI:10.1016/j.ijbiomac.2021.09.017