Estudos in silico dos modos de ligação dos hormônios tireoidianos T3 e T4 com a Proteína Transportadora Albumina Sérica Humana HSA
Abstract
In the present work, the binding mode and molecular interactions between thyroid
hormones (T4, T3 and the positional isomers of T3 – T3IP) and the transporter protein (HSA)
were investigated. T4 has 4 iodine atoms and T3 has 3. Analysis of the crystallographic
structures of the T4-HSA complexes (1HK1,1HK2-R218H, 1HK3-R218P - with fatty acids and
1HK4, 1HK5-R218H- without fatty acids) was carried out. The knowledge acquired was used
in the study of molecular docking to understand T3 since there is no crystallographic
structure of HSA with T3, with T3 being the active form of thyroid hormone in target cells.
It was observed that HSA is capable of differentiating T4 from T3. Another important point
was to study 3 cases of HSA-T4 and HSA-T3 complexes, R128, R218H, R218P and explain the
difference in HSA-hormonal ligand affinity. In the case of the T3 ligand, which has 3 iodine
atoms, with a specific position, 4 positional isomers, T3IP, were evaluated. Docking studies
showed that these compounds are different compared to HSA. The presence of fatty acids
in the crystallographic complexes of the native protein and R218H mutant protein affected
the availability of binding sites, limiting the interaction with T4 to a single site (Cleft). The
analysis of T3 positional isomers (T3IP) showed that the structural flexibility of the ligands
is an important factor in determining interactions with HSA. The findings of this study can
be applied in the development of therapeutic strategies aimed at transporting thyroid
hormones in conditions of genetic mutations or metabolic disorders. Detailed
understanding of the differences in affinity between T3 and T4 and the influence of
mutations in HSA provides a solid basis for future research focused on modulating the
bioavailability of these hormones. The results presented here serve as a starting point for
experimental investigations that can validate the trends observed in silico studies and
explore new applications in the field of endocrinology and biotechnology.
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