Amino Acids (Feb 2025)

L-tyrosine inhibits the formation of amyloid fibers of human lysozyme at physiological pH and temperature

  • Santos López,
  • Arturo Rojo-Domínguez,
  • Roxana López-Simeon,
  • Alejandro Sosa-Peinado,
  • Hugo Nájera

DOI
https://doi.org/10.1007/s00726-025-03445-6
Journal volume & issue
Vol. 57, no. 1
pp. 1 – 12

Abstract

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Abstract Amyloid fibers are implicated in numerous diseases, making their study crucial for identifying effective therapeutic compounds. This research highlights the ability of L-tyrosine to inhibit the formation of amyloid fibers in human lysozyme. At a 1:1 molar ratio under physiological conditions (pH 7.4, 37 °C), L-tyrosine significantly reduces amyloid fiber formation, as evidenced by a decrease in thioflavin T fluorescence. Differential scanning calorimetry (DSC) shows a major energy requirement for temperature denaturation when the lysozyme is in the presence of L-tyrosine. Additionally, chemical denaturation experiments reveal a shift in the intrinsic fluorescence spectrum of lysozyme in the presence of L-tyrosine, indicating a direct interaction. Computational docking studies with Molecular Operating Environment (MOE) further confirm that L-tyrosine binds effectively, exhibiting similar binding energies to those of the natural substrate. This study underscores L-tyrosine’s potential as a strong inhibitor of amyloid fiber formation, demonstrating its stabilizing effect on lysozyme and its promise in therapeutic applications.

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