Article
In silico investigation of riboswitches in fungi: structural and dynamical insights into TPP riboswitches in Aspergillus oryzae
Registro en:
VARGAS JUNIOR, Valdemir et al. In silico investigation of riboswitches in fungi: structural and dynamical insights into TPP riboswitches in Aspergillus oryzae. RNA Biology, v. 19, n. 1, p. 90-103, 2022.
1555-8584
10.1080/15476286.2021.2015174
Autor
Vargas-Junior, Valdemir
Antunes, Deborah
Guimarães, Ana Carolina
Caffarena, Ernesto
Resumen
Riboswitches are RNA sensors affecting post-transcriptional processes through their ability to bind to
small molecules. Thiamine pyrophosphate (TPP) riboswitch plays a crucial role in regulating genes
involved in synthesizing or transporting thiamine and phosphorylated derivatives in bacteria, archaea,
plants, and fungi. Although TPP riboswitch is reasonably well known in bacteria, there is a gap in the
knowledge of the fungal TPP riboswitches structure and dynamics, involving mainly sequence variation
and TPP interaction with the aptamers. On the other hand, the increase of fungal infections and
antifungal resistance raises the need for new antifungal therapies. In this work, we used computational
approaches to build three-dimensional models for the three TPP riboswitches identified in Aspergillus
oryzae, in which we studied their structure, dynamics, and binding free energy change (ΔGbind) with TPP.
Interaction patterns between the TPP and the surrounding nucleotides were conserved among the three
models, evidencing high structural conservation. Furthermore, we show that the TPP riboswitch from
the A. oryzae NMT1 gene behaves similarly to the E. coli thiA gene concerning the ΔGbind. In contrast,
mutations in the fungal TPP riboswitches from THI4 and the nucleoside transporter genes led to
structural differences, affecting the binding-site volume, hydrogen bond occupancy, and ΔGbind.
Besides, the number of water molecules surrounding TPP influenced the ΔGbind considerably. Notably,
our ΔGbind estimation agreed with previous experimental data, reinforcing the relationship between
sequence conservation and TPP interaction.