Molecular insights into the inhibitory potential of anthocyanidins on glucokinase regulatory protein.

Computational methods were used to investigate six anthocyanidins exhibiting antidiabetic activity by inhibiting glucokinase regulatory protein (GKRP) activity. Density functional theory was used to optimise the geometry of anthocyanidins and calculate their quantum chemical properties. A blind docking method was employed to conduct a molecular docking study, which revealed that delphinidin (Del), cyanidin (Cya), and pelargonidin (Pel) as potential GKRP inhibitors with the lowest binding free energy of -8.7, -8.6, and -8.6 kcal/mol, corresponding to high binding affinity. The molecular dynamics study further verified the blind docking results by showing high GKRP-F1P complex stability and high binding affinity calculated through the MM/GBSA method, upon the binding of pelargonidin. The lower RMSF values of pivotal GK-interacting residues for GKRP-F1P-Pel compared to GKRP-F1P, as a positive control, indicating pelargonidin ability to maintain the inactive conformation of GKRP through the inhibition of GK binding. The key residues that control the binding of the F1P to GKRP and anthocyanidin to GKRP-F1P were also identified in this study. Altogether, pelargonidin is anthocyanidins-derived natural products that have the most potential to act as inhibitors of GKRP and as antidiabetic nutraceuticals.

DNA cleavage by oxymyoglobin and cysteine-introduced metmyoglobin.

Double stranded DNA was cleaved oxidatively by incubation with oxygenated myoglobin, and Lys96Cys sperm whale myoglobin in its stable ferric form functioned as an artificial nuclease under air by formation of an oxygenated species, owing to electron transfer from the SH group of the introduced cysteine to the heme.

Morphological change of cell membrane by interaction with domain-swapped cytochrome c oligomers.

Monomeric cyt c has been reported to bind to the mitochondrial membrane by electrostatic and hydrophobic interactions with anionic phospholipids. We have previously shown that domain-swapped oligomeric cyt c retains the secondary structure of the monomer, and its surface possesses a larger area and more charges compared to the monomer. However, the effect of oligomerization of cyt c on cells has yet to be revealed. Herein, we investigated the interaction of oligomeric cyt c with anionic phospholipid-containing vesicles and the outer membrane of HeLa cells. Oligomeric cyt c interacted more strongly than monomeric cyt c with anionic phospholipid-containing vesicles and the outer membrane of HeLa cells. Oligomeric cyt c induced lateral phase separation of lipids in LUVs and GUVs, thereby leading to membrane disruption, whereas monomeric cyt c did not. Morphological changes in HeLa cells resulted from interaction with oligomeric cyt c, but little from interaction with the monomer. These results show that domain-swapped oligomeric proteins might exhibit properties different to those of monomer in cell systems.