5JY0

Crystal structure of Porphyromonas endodontalis DPP11 in complex with substrate

Summary for 5JY0

• Entry DOI: 10.2210/pdb5jy0/pdb
• Descriptor: Asp/Glu-specific dipeptidyl-peptidase, LEU-ASP-VAL, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (4 entities in total)
• Functional Keywords: peptidase, bacterial enzyme, hydrolase
• Biological source: Porphyromonas endodontalis; More
• Cellular location: Secreted : F8WQK8
• Total number of polymer chains: 2
• Total formula weight: 80339.03

Authors

Bezerra, G.A.,Cornaciu, I.,Hoffmann, G.,Djinovic-Carugo, K.,Marquez, J.A. (deposition date: 2016-05-13, release date: 2017-06-14, Last modification date: 2017-06-21)

Primary citation

Bezerra, G.A.,Ohara-Nemoto, Y.,Cornaciu, I.,Fedosyuk, S.,Hoffmann, G.,Round, A.,Marquez, J.A.,Nemoto, T.K.,Djinovic-Carugo, K.
Bacterial protease uses distinct thermodynamic signatures for substrate recognition.
Sci Rep, 7:2848-2848, 2017

PubMed Abstract: 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.

PubMed: 28588213
DOI: 10.1038/s41598-017-03220-y

Experimental method

X-RAY DIFFRACTION (2.599 Å)