# Cullin-3 proteins be a novel biomarkers and therapeutic targets for hyperchloremia induced by oral poisoning

## TL;DR

This study explores Cullin-3 proteins as potential biomarkers and drug targets for hyperchloremia caused by oral poisoning.

## Contribution

The study identifies Cullin-3 as a novel biomarker and drug target for hyperchloremia through genome-wide and molecular analysis.

## Key findings

- Cullin-3 protein showed the highest connectivity in the protein–protein interaction network with 18 nodes.
- Molecular docking results indicate Cullin-3 has low binding energy scores, suggesting potential drug binding.
- Simulations showed Cullin-3 remains stable in both unbound and peptide-bound states over 50 ns.

## Abstract

Oral poisoning can trigger diverse physiological reactions, determined by the toxic substance involved. One such consequence is hyperchloremia, characterized by an elevated level of chloride in the blood and leads to kidney damage and impairing chloride ion regulation. Here, we conducted a comprehensive genome-wide analysis to investigate genes or proteins linked to hyperchloremia. Our analysis included functional enrichment, protein–protein interactions, gene expression, exploration of molecular pathways, and the identification of potential shared genetic factors contributing to the development of hyperchloremia. Functional enrichment analysis revealed that oral poisoning owing hyperchloremia is associated with 4 proteins e.g. Kelch-like protein 3, Serine/threonine-protein kinase WNK4, Serine/threonine-protein kinase WNK1 and Cullin-3. The protein–protein interaction network revealed Cullin-3 as an exceptional protein, displaying a maximum connection of 18 nodes. Insufficient data from transcriptomic analysis indicates that there are lack of information having direct associations between these proteins and human-related functions to oral poisoning, hyperchloremia, or metabolic acidosis. The metabolic pathway of Cullin-3 protein revealed that the derivative is Sulfonamide which play role in, increasing urine output, and metabolic acidosis resulted in hypertension. Based on molecular docking results analysis it found that Cullin-3 proteins has the lowest binding energies score and being suitable proteins. Moreover, no major variations were observed in unbound Cullin-3 and all three peptide bound complexes shows that all systems remain compact during 50 ns simulations. The results of our study revealed Cullin-3 proteins be a strong foundation for the development of potential drug targets or biomarker for future studies.