Investigation of Silent Information Regulator 1 (Sirt1) Agonists from Traditional Chinese Medicine
Kuan-Chung Chen, Yi-Ru Jian, Mao-Feng Sun, Tung-Ti Chang, Cheng-Chun Lee & Calvin Yu-Chian Chen [1]
Molecular Tour
is classified as nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase. It catalyzes the deacetylation reaction of proteins and cleavage of NAD into nicotinamide and 1-O-acetyl-ADP ribose, which plays an important role in regulating metabolic signaling pathways in various organisms. Sirt1 is a potential target protein for diseases associated with aging.
The structure of Sirt1 protein for virtual screening is generated using Homology Modeling with the sequence of Human Sirt1 (UniProtKB: Q96EB6) and the template proteins of Human SirT2 (PDB: 1j8f), Human SirT5 (PDB: 2nyr), Archaeoglobus fulgidus Sir2 (PDB: 1ici), Yeast Sir2 (PDB: 1q17), and the protein produced by I-TASSER. The definition of (colored in green) and key active residue (colored in magenta) in the catalytic domain indicated by Medda et al study [2].
In silico results indicate that traditional Chinese medicine compounds (colored in purple), (colored in orange), and (colored in yellow) had high binding affinity with Sirt1 protein and formed hydrogen bonds with residue Ser442 and other residues in the Sirt1 binding site (colored in cyan). The top TCM candidates, (S)-tryptophan-betaxanthin, 5-O-feruloylquinic acid, and RosA, may have potential to be lead compounds for diseases associated with aging.
