Porphyromonas gingivalis and Porphyromonas endodontalis are important bacteria related to periodontitis， the most common chronic inflammatory disease in humans worldwide. Its comorbidity with systemic diseases， such as type 2 diabetes， oral cancers and cardiovascular diseases， continues to generate considerable interest. Surprisingly， these two microorganisms do not ferment carbohydrates; rather they use proteinaceous substrates as carbon and energy sources. However， the underlying biochemical mechanisms of their energy metabolism remain unknown. Here， we show that dipeptidyl peptidase 11 (DPP11)， a central metabolic enzyme in these bacteria， undergoes a conformational change upon peptide binding to distinguish substrates from end products. It binds substrates through an entropy-driven process and end products in an enthalpy-driven fashion. We show that increase in protein conformational entropy is the main-driving force for substrate binding via the unfolding of specific regions of the enzyme ("entropy reservoirs"). The relationship between our structural and thermodynamics data yields a distinct model for protein-protein interactions where protein conformational entropy modulates the binding free-energy. Further， our findings provide a framework for the structure-based design of specific DPP11 inhibitors.