Biochemical and Crystallographic Analyses of Proteins Related to Butyrate Synthesis and peptide Transport in Periodontal Disease-Implicated Bacteria

Periodontal disease (PD) is associated with harmful oral biofilm development, including the red complex bacteria: Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. PD presents as gum inflammation, periodontal pocket formation, edentulism, and other adverse health effects. Various gene products are upregulated during infection, suggesting involvement of those genes in periodontopathology. However, specific etiological mechanisms remain poorly understood. By undertaking gene product characterization, this research aims to expand our etiological knowledge. In P. gingivalis, a dehydrogenase, involved in butyrate synthesis was investigated. Kinetic assays confirm dehydrogenation activity while structural data revealed various features such as catalytic and oligomerization domains connected by a linker motif. In T. denticola, the structure and ligand preference of a peptide-binding protein was investigated. Thermostability shift assays revealed a moderate affinity for a series of peptides, with some compositional preference while structural data revealed a conserved peptide-binding motif. Overall, this research informs the role of PD related proteins in the synthesis of butyrate and as an oligopeptide binding protein, with various important structural features highlighted. In tandem, these proteins contribute to periodontal tissue damage and immune cell disruption, thus contributing to PD progression.