Screening of Human Proteins for Fluoride and Aluminum Binding

Abstract

Previous studies showed that prolonged exposure to fluoride (F-) and aluminum (Al3+) ions is associated with numerous diseases including neurological disorders. They don't have any known biological function. But they can bind with proteins that interact with ions similar to them. Such unwanted interactions affect the normal biological function of the target proteins, as well as their downstream protein-protein interactions. Several studies show the detrimental effects posed by them including Alzheimer's disease. However, their target proteins have never been reported. Here, we have screened for the human protein targets subjected to F- and Al3+ interactions by using data-driven prediction tools. We have identified 20 different proteins that directly bind with them (10 interact with fluoride and 10 with aluminum). In addition, protein-protein interaction has been explored to find the proteins that indirectly interact with F- and Al3+. We have found 86 indirect targets for F- and 90 for Al3+. Furthermore, 19 common protein targets have been identified, including proteins (9 out of 19) associated with neurodegenerative disorders. However, wet lab experiments are beyond our scopes to validate the binding networks. Additional studies must be warranted.

Long-term exposure to environmentally relevant concentrations of ibuprofen and aluminum alters oxidative stress status on Danio rerio

“…This behavior might partly explain that even though increasing values of superoxide J o u r n a l P r e -p r o o f dismutase and glutathione peroxidase were found mainly for binary mixtures in certain tissues at specific times of exposure in the present study, significantly increased values of lipid peroxidation were also observed. Hasan et al (2018) detected that Al ions were capable of interact (ion-protein/ protein-protein) affecting the normal biological function of target proteins including antioxidant enzymes CAT and GPX with the subsequent loss of catalytic function.…”

Developmental alterations, teratogenic effects, and oxidative disruption induced by ibuprofen, aluminum, and their binary mixture on Danio rerio

“…Once this metal penetrates the chorion, it can bind the thiol J o u r n a l P r e -p r o o f groups of proteins and induce the formation of radical species, responsible for embryotoxic effects in various aquatic organisms (Adeyemi et al, 2015;Ganesan et al, 2016). García-Medina et al, (2010) and Hasan et al, (2018) reported that this metal affects electron transport in the respiratory chain because of direct damage to mitochondria and interact in a direct (ionprotein) and indirect (protein-protein) way with various proteins and enzymes essential for several biological processes as well as molecular functions in different organisms. Further, skeletal abnormalities, mainly tail and craniofacial malformations found in the present study may be explained as Al may accumulate in bones as it displaces calcium on the bone surface, leading to aberrations in mineralization, hypercalcemia, hypercalciuria, and osteomalacia.…”

Synthesis of Phthalimide Imine Derivatives as a Potential Anticancer Agent

“…e underlying mechanisms of these effects are still unclear; however, higher rates of lipophilicity, cellular permeability, and intermolecular bonds with biomolecules constitute probable explanatory axes [42]. On the other hand, fluorine has been reported to own the strongest hydrogen binding among halogens, which enable selective binding to specific proteins or enzymes, hence providing good anticancer activity [30,[43][44][45].…”