Interaction of fumigaclavine C with High Mobility Group Box 1 protein (HMGB1) and its DNA complex: A computational approach.

Interaction of fumigaclavine C with High Mobility Group Box 1 protein (HMGB1) and its DNA complex: A computational approach. Comput Biol Chem. 2020 Oct 31;89:107409 Authors: Bailly C, Vergoten G Abstract The fumigaclavines represent a small group of clavine-type alkaloids produced by the pathogenic fungus Aspergillus fumigatus. The leading compound in the family is fumigaclavine C (Fm-C) endowed with potent anti-inflammatory properties. Fm-C represses the production of several inflammatory cytokines in cells via a mechanism implicating a reduced nucleo-cytoplasmic transport and extracellular export of the alarmin protein HMGB1, through a direct drug-protein interaction, and a down-regulation of HMGB1 expression. We have investigated the interaction of Fm-C with HMGB1 using two complementary forms of the HMG-box protein, in its free and DNA-bound configurations, using molecular modeling. We identified up to six potential binding sites for Fm-C in the vicinity of the B-box of HMGB1, with the site designated Lys-103 being the most favored and maintained when the protein is bound to a 16-base pair DNA oligonucleotide. Structure-binding relationships have been explored through the comparison of the HMGB1-binding properties of fumigaclavines A, B and C, and the related alkaloid lysergic acid diethylamide (LSD). Both the C-9 acetyl group and C-2 dimethylallyl side chain of Fm-C contribute importantly to the protein interaction. LSD appears ...
Source: Computational Biology and Chemistry - Category: Bioinformatics Authors: Tags: Comput Biol Chem Source Type: research