Abstract
Introduction Neuropsychiatric syndromes have an important connection with disorders in the regulation
of serotonin, with human tryptophan hydroxylase-2 being one of the related biosynthetic
enzymes of this neurotransmitter. Evidence-based genetic studies suggest a possible
involvement of this enzyme in neuropsychiatric disorders caused by abnormalities in
the synthesis and regulation of serotonin.
Objective To analyze the structural effects of single nucleotide polymorphism (SNP) in the
enzyme tryptophan hydroxylase-2 and the changes that lead to functional alterations.
Materials and Methods In this study, we performed an in silico analysis of SNPs associated with abnormal
folding of the tryptophan hydroxylase-2 protein. Different programs were used to identify
amino acid changes evidencing pathogenic effects and possible functional impairments.
Results A change in the amino acid 341 (lysine [L]for phenylalanine [F]) (L341F) of the protein
chain affects the total enthalpy of the protein. The enthalpy turned positive due
to the energy required for the amino acid to return to its original condition. The
protein function is also affected negatively because of the altered structured.
Conclusion The change in the L341F leads to serious structural defects in the tryptophan hydroxylase-2.
Those defects can be further related with functional instability and associated to
the etiology of neuropsychiatric diseases.
Keywords
polymorphism - serotonin - tryptophan hydroxylase - SNPs - amino acid
