Poster Presentation 9th General Meeting of the International Proteolysis Society 2015

Structural and mutational studies of dipeptidyl peptidase 11 from Porphyromonas gingivalis. (#160)

Yasumitsu Sakamoto 1 , Yoshiyuki Suzuki 2 , Ippei Iizuka 1 , Chika Tateoka 1 , Saori Roppongi 1 , Mayu Fujimoto 1 , Koji Inaka 3 , Hiroaki Tnaka 4 , Mitsugu Yamada 5 , Kazunori Ohta 5 , Hiroaki Gouda 6 , Takamasa Nonaka 1 , Wataru Ogasawara 2 , Nobutada Tanaka 6
  1. Iwate Medical University, Yahaba, IWATE, Japan
  2. Nagaoka University of Technology, Nagaoka, Niigata, Japan
  3. MARUWA Foods and Biosciences, Yamatokoriyama, Nara, Japan
  4. Confocal Science, Chiyoda, Tokyo, Japan
  5. Japan Aerospace Exploration Agency, Tsukuba, Ibaraki, Japan
  6. Showa University, Shinagawa, Tokyo, Japan

 Approximately 750 million people worldwide are infected with chronic periodontitis. Periodontitis is caused by periodontal pathogens such as Porphyromonas gingivalis, Porphyromonas endodontalis and others. Most of Periodontal pathogens are gram-negative asaccharolytic (non-fermenting) bacteria. These pathogens utilize protein or peptide as carbon or energy source.　Especially, Transporting dipeptides from Periplasm to Cytoplasm is a very important step in peptide metabolism, because of inner membrane preferentially transports dipeptide rather than an amino acid.  Dipeptidyl peptidases (DPPs) are involved in the dipeptide production in peptide metabolism.  DPPs in Periplasm are consists of DPP4, DPP5, DPP7 and DPP11.  DPP4 and DPP5, DPP7 and DPP11 belong to Clan SC Family S9, Clan PA Family S46 in the MEROPS database, respectively.  The Family S9 peptidases are widely distributed from prokaryotes to eukaryotes. On the other hands, The Family S46 peptidases are distributed in anaerobic gram-negative bacteria, but they are not found in mammals. DPP11 produces dipeptides from N-terminus of peptides with a glutamate or aspartate residue at the penultimate position. Here we report that first crystal structure of the DPP11 from Porphyromonas gingivalis. This structure study could be useful for the structure based drug design for specific inhibitors of DPP11s from pathogens.

  1. Sakamoto Y. et al. Structural and mutational analyses of dipeptidyl peptidase 11 from Porphyromonas gingivalis reveal the molecular basis for strict substrate specificity. Sci. Rep. 5:11151 (2015)
  2. Ohara-Nemoto et al. Asp- and Glu-specific novel dipeptidyl peptidase 11 of Porphyromonas gingivalis ensures utilization of proteinaceous energy sources. J. Biol. Chem. 286:38115-27 (2011)