Fig 1.
A comprehensive examination of the Wnt/β-catenin signaling pathway.
Eliminating the presence of Wnt ligands (“WNT OFF”), the destruction complex phosphorylates cytosolic β-catenin, leading to its recognition and subsequent proteasomal breakdown. When Wnt ligands are present (“WNT ON”), The main purpose of the “destruction complex” is prevented in the intent to phosphorylate cytosolic β-catenin. The introduction of β-catenin that is not phosphorylated in the cytosol causes it to go into the nucleus, which results in the production of Wnt target genes which results in the T-cell factor along with lymphoid enhancer factor-1 (TCF/LEF1) family associated with transcription factors [14].
Fig 2.
Structure of Doxorubicin and Zinc conjugated with Doxorubicin.
Fig 3.
Protein Interaction Network of CTNNB1 (β-catenin) using String database.
Fig 4.
Distance analysis between Lys312 ofβ-catenin and Glu24 of Tcf-4
(A) prior to docking (B) presence of absence of Doxorubicin and (C) after binding with Zn-Doxorubicin.
Table 1.
Angles and Hydrogen bond measurements for β-catenin/Tcf-4 complex.
Fig 5.
(A) Zn-Doxorubicin–1JDH (B) Doxorubicin–1JDH. In both (a) and (b), the Trp383 shows pi-Alkyl and π-π stacked interactions.
Fig 6.
Average interaction ofβ-catenin and Doxorubicin contact at the binding site.
The region is stabilized in the presence of water molecules and the charged residues.
Fig 7.
Average Interaction of Protein-Zn-Doxorubicin Complex.
The region is stabilized with the hydrophobic residues such as Phe21 and Ile19.
Table 2.
The relative binding energies obtained by MM/GBSA.
Table 3.
Binding energy at various level of theory in gas phase for ligand-amino acid complexes.
Fig 8.
(a) Optimized structure of Doxorubicin – protein complex and (b) Zn-Doxorubicin bounds with amino acids. Frontier molecular orbital diagram of Doxorubicin and Zn-Doxorubicin with amino acids obtained in gas phase at B3LYP/6-31g(d) level.
Table 4.
FMO energies of optimized structures of Doxorubicin and Zn-Doxorubicin at various levels in gas phase.
Fig 9.
a) Doxorubicin–amino acids (monomer) and b) Zn-Doxorubicin–amino acids (monomer).
Fig 10.
The docked structure was superimposed to distinguish the binding of Doxorubicin (yellow) and Zn – Doxorubicin (blue).