X-Meeting presentations

TYPE 1 IP3 RECEPTOR IN SACCHAROMYCES CEREVISIAE: IDENTIFICATION THROUGH MOLECULAR MODELING

Published in 21/11/2024 - ISBN: 978-65-272-0843-3

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Paper Title
TYPE 1 IP3 RECEPTOR IN SACCHAROMYCES CEREVISIAE: IDENTIFICATION THROUGH MOLECULAR MODELING
Authors
  • Sayonara Quaresma Alves Campos
  • Rodrigo Bentes Kato
  • Bruno Silva Andrade
  • Raquel D. Penido
  • Lorena Freitas
  • Ruana Carolina Cabral da Silva
  • Aureliano Claret da Cunha
  • Rogélio Lopes Brandão
  • Izinara Rosse da Cruz
Modality
Poster
Subject area
Proteins and Proteomics
Publishing Date
21/11/2024
Country of Publishing
Brazil | Brasil
Language of Publishing
Inglês
Paper Page
https://www.even3.com.br/anais/xmeeting-2024/836594-type-1-ip3-receptor-in-saccharomyces-cerevisiae--identification-through-molecular-modeling
ISBN
978-65-272-0843-3
Keywords
molecular docking, active site, molecular dynamics, type 1 IP3 receptor
Summary
Saccharomyces cerevisiae, a crucial microorganism in various biotechnological applications. It has in its cytoplasmic membrane the protein H+-ATPase, coded by the gene PMA1, which plays a regulatory role in the physiology of fungi and fermentation processes. The pathway of activation of H+-ATPase has been studied over the years, however, has not yet been fully elucidated. Although there is evidence of interaction between calcium signaling, H+-ATPase activation and inositol 1.4,5-trifosphate (IP3) molecules this interaction has not been fully characterized. Previous studies in our group have shown that the deletion of the ARG82 gene increases the concentration of cytoplasmic IP3 in the yeast. IP3 then binds to an unknown receptor, increasing the release of Ca2+, promoting greater activation of H+-ATPase. It is known that in higher eukaryotes the IP3 receptors have the function of regulating cytoplasmic Ca2+ signals. In addition, in plant cells, IP3 acts as a second messenger that modules the release of Ca2+ from vacuole. In S. cerevisiae this function is performed by the Yvc1 calcium channel present in the vacuum that presents a two-phase response, where Ca2+ in conjunction with an unknown molecule promotes the opening of the channel. This evidence raised the hypothesis that IP3 would connect directly to Yvc1p. The Yvc1p was obtained from the Protein Database (PDB) and the molecule IP3, in the yeast metabolome database (YMDB). A common region for the construction of the gridbox was defined by identifying residues preserved in the protein IP3R1 in other species, and then comparing them with a sequence of Yvc1p. To confirm the hypothesis, docking studies were conducted using the DockThor, where the candidate region was defined considering the greater number of hydrogen bonds and most negative interaction energy. In addition, Root Mean Square Deviation (RMSD) values were considered for re-docking validations, with values below 2 Å. The best poses were submitted to molecular dynamics using GROMACS for 100 nanoseconds, and the existence of a binding site for the IP3 molecule on Yvc1p was demonstrated, showing persistent interaction with the binding site of the Yvc1 protein. mCSM software was used to identify amino acids with the highest destabilizing capacity of the identified site. Subsequently, new Yvc1p structures were generated using SWISS-MODEL. Models generated with the mutations S342D; K335S; K258D; R339S; R329G and R339H, demonstrated that, the occurrence of mutations in the region identified as IP3 binding site in Yvc1p, can modify the site, resulting in the loss of the interaction between the molecule and the region. Thus, the linkages established between IP3 and Yvc1p are promising, since by introducing mutations in specific amino acids the interaction of IP3 was inhibited in the site region. According to the results, it is possible to point out that IP3 can bind directly to Yvc1p. This result indicates, for the first time, a candidate protein to be one of the IP3 receptors in S. cerevisiae. These results have a great biotechnological impact since the increase in enzyme activity is directly related to the improvement of the fermentation process.
Title of the Event
20º Congresso Brasileiro de Bioinformática: X-Meeting 2024
City of the Event
Salvador
Title of the Proceedings of the event
X-Meeting presentations
Name of the Publisher
Even3
Means of Dissemination
Meio Digital

How to cite

CAMPOS, Sayonara Quaresma Alves et al.. TYPE 1 IP3 RECEPTOR IN SACCHAROMYCES CEREVISIAE: IDENTIFICATION THROUGH MOLECULAR MODELING.. In: X-Meeting presentations. Anais...Salvador(BA) Hotel Deville Prime, 2024. Available in: https//www.even3.com.br/anais/xmeeting-2024/836594-TYPE-1-IP3-RECEPTOR-IN-SACCHAROMYCES-CEREVISIAE--IDENTIFICATION-THROUGH-MOLECULAR-MODELING. Access in: 06/12/2025

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