Structural insight into the ligand-receptor interaction between glycyrrhetinic acid (GA) and the high-mobility group protein B1 (HMGB1)-DNA complex

Structural analysis of the high-mobility group protein B1 (HMGB1)-DNA complex and a docking simulation betweenglycyrrhetinic acid (GA) and the HMGB1-DNA complex were performed with a software package the Molecular OperatingEnvironment (MOE). An HMGB1-DNA (PDB code: 2GZK) was selected for the 3D structure modeling of the HMGB1-DNAcomplex. The Site Finder module of the MOE identified 16 possible ligand-binding sites in the modeled HMGB1-DNA complex.The docking simulation revealed that GA possibly inhibits functions of HMGB1 interfering with Lys₉₀, Arg₉₁, Ser₁₀₁, Tyr₁₄₉, C₂₃₀ andC₂₃₁ in the HMGB1-DNA complex. To the best of our knowledge, this is the first report of an HMGB1-DNA complex with GA, andour data verify that the GA-HMGB1-DNA model can be utilized for application to target HMGB1 for the development of antitumordrugs.

Abbreviations

ASE-Dock - alpha sphere and excluded volume-based ligand-protein docking, CNS - central nervous system, GA - glycyrrhetinic acid, GL - glycyrrhizin, HMGB1 - high-mobility group protein B1, LBS - ligand-biding site, MOE - Molecular Operating Environment, SRY - sex-determining region on the Y chromosome.