5JXP

Crystal structure of Porphyromonas endodontalis DPP11 in alternate conformation

5JXP の概要

• エントリーDOI: 10.2210/pdb5jxp/pdb
• 分子名称: Asp/Glu-specific dipeptidyl-peptidase, CALCIUM ION, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: peptidase, bacterial enzyme, hydrolase
• 由来する生物種: Porphyromonas endodontalis (strain ATCC 35406 / BCRC 14492 / JCM 8526 / HG 370)
• 細胞内の位置: Secreted : F8WQK8
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 79860.34

構造登録者

Bezerra, G.A.,Cornaciu, I.,Hoffmann, G.,Djinovic-Carugo, K.,Marquez, J.A. (登録日: 2016-05-13, 公開日: 2017-06-14, 最終更新日: 2017-06-21)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.5 Å)