Effect of pH on the structure and stability of irisin, a multifunctional protein: Multispectroscopic and molecular dynamics simulation approach

Waseem, Rashid; Shamsi, Anas; Shahbaz, M.; Khan, Tanzeel; Kazim, Syed Naqui; Ahmad, Faizan; Hassan, Md. Imtaiyaz; Islam, Asimul

doi:10.1016/j.molstruc.2021.132141

Cited by 11 publications

(5 citation statements)

References 40 publications

(31 reference statements)

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“…Fluorescence emission spectra of free irisin and irisin with different concentrations of fluoxetine (0–30 µM), memantine (0–24 µM), and galantamine (0–20 µM) are shown in Figure 2 . The native irisin shows fluorescence emission maxima around 344 nm [ 28 ]. The fluorescence quenching of irisin was observed with increasing ligand concentrations for all three drugs.…”

Section: Resultsmentioning

confidence: 99%

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Unraveling the Binding Mechanism of Alzheimer’s Drugs with Irisin: Spectroscopic, Calorimetric, and Computational Approaches

Waseem

Shamsi

Khan

et al. 2022

IJMS

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The prevalence of Alzheimer’s disease (AD) has been a major health concern for a long time. Despite recent progress, there is still a strong need to develop effective disease-modifying therapies. Several drugs have already been approved to retard the progression of AD-related symptoms; however, there is a need to develop an effective carrier system for the delivery of drugs to combat such diseases. In recent years, various biological macromolecules, including proteins, have been used as carriers for drug delivery. Irisin is a beneficial hormone in such diseases, including AD and related pathologies. Herein, the interaction mechanism of irisin with AD drugs such as memantine, galantamine, and fluoxetine is investigated. Fluorescence studies revealed that the above drugs bind to irisin with significant affinity, with fluoxetine having the highest binding affinity. Isothermal titration calorimetry (ITC) complemented the spontaneous binding of these drugs with irisin, delineating various associated thermodynamic and binding parameters. Molecular docking further validated the fluorescence and ITC results and unfolded the mechanism that hydrogen bonding governs the binding of fluoxetine to irisin with a significant binding score, i.e., −6.3 kcal/mol. We believe that these findings provide a promising solution to fight against AD as well as a platform for further research to utilize irisin in the drug-delivery system for an effective therapeutic strategy.

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Section: Resultsmentioning

confidence: 99%

“…Irisin was purified according to previously published reports [ 26 , 28 ]. In brief, the expression construct of irisin was transformed in E. coli C41-DE3 cells.…”

Section: Methodsmentioning

confidence: 99%

Unraveling the Binding Mechanism of Alzheimer’s Drugs with Irisin: Spectroscopic, Calorimetric, and Computational Approaches

Waseem

Shamsi

Khan

et al. 2022

IJMS

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“…The native irisin shows a negative peak at around 218 nm, which is suggestive of the fact that irisin is a β-rich protein. 28,50 CD spectra of irisin incubated with MG (5 m and 10 mM) show a marked increase in dichroic signal as a function of time (Figure 4). This increase in CD signal implies that MG causes structural changes in protein with the increase in β-sheet content.…”

Section: Spectroscopymentioning

confidence: 99%

Characterization of advanced glycation end products and aggregates of irisin: Multispectroscopic and microscopic approaches

Waseem

Shamsi

Khan

et al. 2022

J of Cellular Biochemistry

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Glycation of proteins leading to the formation of advanced glycation end products (AGEs) has been demonstrated to contribute to the pathogenesis of several diseases. Irisin is a clinically significant protein, putatively involved in obesity, diabetes, and neurological disorders. This study aimed to monitor the methyl-glyoxal (MG) induced AGEs and aggregate formation of irisin, as a function of time, employing multispectroscopic and microscopic approaches.ANS fluorescence suggested a molten globule-like state on Day 6, followed by the formation of irisin AGEs adducts, as confirmed by AGE-specific fluorescence. Glycation of irisin led to aggregate formation, which was characterized by Thioflavin T fluorescence, CD spectroscopy, and microscopic studies. These aggregates were confirmed by exploiting fluorescence microscopy, confocal, and transmission electron microscopy. Molecular docking was performed to determine the crucial residues of irisin involved in irisin-MG interaction. Usually, MG is present in trace amounts as a metabolic by-product in the body, which is found to be elevated in diseased conditions viz. diabetes and Alzheimer's disease. This study characterized the AGEs and aggregates of clinically important protein, irisin; and since MG level has been found to be increased in various pathological conditions, this study provides a clinical perspective. There is a possibility that elevated MG concentrations might glycate irisin resulting in reduced irisin levels as reported in pathological conditions. However, further investigations are required to prove it.

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“…It is known that a kinase, MARK4, is associated with different cancers and uncontrolled neural migration, and is a potential therapeutic drug target for cancer and AD therapy. On the other hand, irisin is identified as a potential therapeutic agent against AD [ 33 , 76 ]. We have recently shown through a protein–protein interaction study that irisin can inhibit the MARK4 via binding with an excellent affinity and subsequently inhibit its activity [ 61 ].…”

Section: The Role Of Irisin In Human Pathophysiologymentioning

confidence: 99%

FNDC5/Irisin: Physiology and Pathophysiology

et al. 2022

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A sedentary lifestyle or lack of physical activity increases the risk of different diseases, including obesity, diabetes, heart diseases, certain types of cancers, and some neurological diseases. Physical exercise helps improve quality of life and reduces the risk of many diseases. Irisin, a hormone induced by exercise, is a fragmented product of FNDC5 (a cell membrane protein) and acts as a linkage between muscles and other tissues. Over the past decade, it has become clear that irisin is a molecular mimic of exercise and shows various beneficial effects, such as browning of adipocytes, modulation of metabolic processes, regulation of bone metabolism, and functioning of the nervous system. Irisin has a role in carcinogenesis; numerous studies have shown its impact on migration, invasion, and proliferation of cancer cells. The receptor of irisin is not completely known; however, in some tissues it probably acts via a specific class of integrin receptors. Here, we review research from the past decade that has identified irisin as a potential therapeutic agent in the prevention or treatment of various metabolic-related and other diseases. This article delineates structural and biochemical aspects of irisin and provides an insight into the role of irisin in different pathological conditions.

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Effect of pH on the structure and stability of irisin, a multifunctional protein: Multispectroscopic and molecular dynamics simulation approach

Cited by 11 publications

References 40 publications

Unraveling the Binding Mechanism of Alzheimer’s Drugs with Irisin: Spectroscopic, Calorimetric, and Computational Approaches

Unraveling the Binding Mechanism of Alzheimer’s Drugs with Irisin: Spectroscopic, Calorimetric, and Computational Approaches

Characterization of advanced glycation end products and aggregates of irisin: Multispectroscopic and microscopic approaches

FNDC5/Irisin: Physiology and Pathophysiology

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