An insight into the binding and inhibition of eye ζ-crystallin by the environmental toxin arsenic: implications in eye diseases

Abstract

Arsenic contamination is highly prevalent in food chain, soil and groundwater. Continuous exposure to elevated levels of this environmental toxin is a global concern. Studies have reported enriched accumulation of arsenic in the eyes compared to other body organs leading to various eye diseases. Here, the impact of arsenic exposure on the enzymatic eye ζ-crystallin has been investigated. Arsenic inhibited the activity of the enzyme with an IC₅₀ value of 35 µM. It decreased the free thiol group content of ζ-crystallin due to protein oxidation. The binding of arsenic with ζ-crystallin was explored using biophysical and computational tools. The enzyme undergoes some conformational changes upon arsenic binding. The binding constant (K_b) was determined to be 1.2 × 10² M⁻¹. Thermodynamic parameters were determined by isothermal titration calorimetry (ITC) and the binding energy (ΔG) was calculated to be −3.52 kcal/mol. Molecular docking studies helped in visualizing the amino acid residues (especially Cys165) of the enzyme involved in binding with arsenic. Continuous arsenic exposure is expected to increase the eye crystallin-related abnormalities, elevating the risk of cataractogenesis. Therefore, proper measures need to be taken by authorities to control the contamination of arsenic in the environment and groundwater.

Communicated by Ramaswamy H. Sarma

Keywords:

• ζ-crystallin
• arsenic
• inhibition
• eye health

Acknowledgements

Research Facilities provided by the Aligarh Muslim University are gratefully acknowledged.

Disclosure statement

The authors declare that there are no conflicts of interest.

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Author’s contributions

Md Amiruddin Hashmi: Methodology, Investigation, Formal analysis, Writing - original draft. Ajamaluddin Malik: Methodology, Formal analysis, Writing - review and editing. Faizan Abul Qais: Methodology. Masood Alam Khan: Formal analysis, Writing - review and editing. Fahad Abdulrahman Alhumaydhi: Methodology. Hina Younus: Conceptualization, Validation, Formal analysis, Writing - original draft, Writing - review and editing, Visualization, Supervision.