Article ; Online: Evaluation of decursin and its isomer decursinol angelate as potential inhibitors of human glutamate dehydrogenase activity through in silico and enzymatic assay screening.
Computers in biology and medicine
2022 Volume 151, Issue Pt B, Page(s) 106287
Abstract: Glutaminolysis is a typical hallmark of malignant tumors across different cancers. Glutamate dehydrogenase (GDH, GLUD1) is one such enzyme involved in the conversion of glutamate to α-ketoglutarate. High levels of GDH are associated with numerous ... ...
Abstract | Glutaminolysis is a typical hallmark of malignant tumors across different cancers. Glutamate dehydrogenase (GDH, GLUD1) is one such enzyme involved in the conversion of glutamate to α-ketoglutarate. High levels of GDH are associated with numerous diseases and is also a prognostic marker for predicting metastasis in colorectal cancer. Therefore, inhibiting GDH can be a crucial therapeutic target. Here in this study, we performed molecular docking analysis of 8 different plants derived single compounds collected from pubChem database for screening and selected decursin (DN) and decursinol angelate (DA). We performed molecular dynamics simulation (MD), monitored the stability, interaction for protein and docked ligand at 50 ns, and evaluated the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) free energy calculation on the twoselected compounds along with a standard inhibitor epigallocatechin gallate (EGCG) as reference. The final results showed the formation of stable hydrogen bond interactions by DN and DA in the residues of R400 and Y386 at the ADP activation site of GDH, which was important for the selective inhibition of GDH activity. Additionally, the total binding energy of DN and DA were -115.5 kJ/mol and -106.2 kJ/mol, which was higher than the standard reference GDH inhibitor EGCG (-92.8 kJ/mol). Furthermore, biochemical analysis for GDH inhibition substantiated our computational results and established DN and DA as novel GDH inhibitor. The percentage of IC |
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Language | English |
Publishing date | 2022-11-14 |
Publishing country | United States |
Document type | Journal Article |
ZDB-ID | 127557-4 |
ISSN | 1879-0534 ; 0010-4825 |
ISSN (online) | 1879-0534 |
ISSN | 0010-4825 |
DOI | 10.1016/j.compbiomed.2022.106287 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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