Browsing by Author "Srinivasan, Suchita"

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    Analyzing the Effects of Mutating S221L in the Binding of Inhibitor (-)- Huperzine A and Acetylcholine to AChE to Reduce the Impact of Alzheimer's
    Srinivasan, Suchita; Jaber, Batool; Elkady, Mariem; Reyes, Kasey; Bhawan, Priscilla (2024-08-06)
    Alzheimer's disease (AD) continues to pose a growing public health threat across the globe, with its progression leading to severe cognitive decline. A feature of this condition is the reduction of acetylcholine, a neurotransmitter that plays a crucial role in memory and learning. The study hypothesized that mutating S221, a key residue in AChE's active site, to leucine, would disrupt acetylcholine binding and affect the AChE inhibitor (-)-Huperzine A. Leucine was chosen for its similar size to serine but with greater nonpolar character, aiming to change the active site's chemistry without drastically altering its structure. Molecular docking was used to predict the interactions between the mutated enzyme, acetylcholine, and (-)-Huperzine A, highlighting how the mutation impacts binding affinity and inhibitor selectivity. The S221 mutation successfully disrupted substrate binding and reduced enzyme activity, supporting the hypothesis. These findings suggest that modifying the catalytic triad could preserve acetylcholine levels, potentially alleviating AD symptoms. Further research is needed to refine this approach, with proposed studies using site-directed mutagenesis and molecular docking to achieve selective inhibition of acetylcholine binding while retaining inhibitor affinity. This strategy could offer a more significant method for AD treatment with fewer side effects than complete AChE inactivation.