Affiliations: [a] Department of Medical Laboratories, College of Applied Medical Sciences, Shaqra University, Shaqra, Saudi Arabia
| [b] Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha, Saudi Arabia
| [c] Department of Biochemistry, Aligarh Muslim University, Aligarh, India
| [d] Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| [e] Pharmaceutical Sciences Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| [f] Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India
| [g] Center of Medical and Bio-Allied Health Sciences Research (CMBHSR), Ajman University, United Arab Emirates
Correspondence:
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Correspondence to: Anas Shamsi, PhD, MRSB, Center of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman P.O. Box 346, United Arab Emirates. E-mail: [email protected].
Abstract: Background:Neurodegeneration is a term describing an irreversible process of neuronal damage. In recent decades, research efforts have been directed towards deepening our knowledge of numerous neurodegenerative disorders, with a particular focus on conditions such as Alzheimer’s disease (AD). Human transferrin (htf) is a key player in maintaining iron homeostasis within brain cells. Any disturbance in this equilibrium gives rise to the emergence of neurodegenerative diseases and associated pathologies, particularly AD. Limonene, a natural compound found in citrus fruits and various plants, has shown potential neuroprotective properties. Objective:In this study, our goal was to unravel the binding of limonene with htf, with the intention of comprehending the interaction mechanism of limonene with htf. Methods:Binding was scrutinized using fluorescence quenching and UV-Vis spectroscopic analyses. The binding mechanism of limonene was further investigated at the atomic level through molecular docking and extensive 200 ns molecular dynamic simulation (MD) studies. Results:Molecular docking uncovered that limonene interacted extensively with the deep cavity located within the htf binding pocket. MD results indicated that binding of limonene to htf did not induce substantial structural alterations, ultimately forming stable complex. The findings from fluorescence binding indicated a pronounced interaction between limonene and htf, limonene binds to htf with a binding constant (K) of 0.1×105 M–1. UV spectroscopy also advocated stable htf-limonene complex formation. Conclusions:The study deciphered the binding mechanism of limonene with htf, providing a platform to use limonene in AD therapeutics in context of iron homeostasis.
