Structural and functional studies of dipeptidyl aminopeptidases from periodontal pathogen.

• Project/Area Number: 25462872
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Iwate Medical University
• Principal Investigator: SAKAMOTO YASUMITSU 岩手医科大学, 薬学部, 助教 (00349036)
• Co-Investigator(Renkei-kenkyūsha): TANAKA Nobutada 昭和大学, 薬学部, 准教授 (00286866) ; OGASAWARA Wataru 長岡技術科学大学, 工学部, 教授 (40292172)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: DPP11 / S46 / ペプチダーゼ / 抗菌薬 / 結晶構造解析 / 歯周病 / 構造生物学 / DPP / Antibiotics / Perio / S46 peptidase

Outline of Final Research Achievements

The morbidity of periodontal disease is reported to be 50% above in population worldwide. Some Non-Fermenting Gram-Negative Rods (NFGNR) may cause periodontal disease, such as Porphyromonas gingivalis.
NFGNR is well known as that utilize peptides as energy and carbon sources instead of carbohydrates. DPPs (Dipeptidyl aminopeptidase) are peptide degradation enzymes that play a key part in intake of peptides.
Bacterial DPPs are divided into two categories (Clan SC S9, Clan PA S46). Interestingly, DPPs of Clan PA S46 are only found in bacteria. Our X-ray crystallographic studies of Pseudomonas mexicana WO24 DAP BII and Porphyromonas gingivalis DPP11 revealed that catalytic mechanism and substrate recognition mechanism. These findings are useful in the development of specific inhibitors for S46 peptidases.

Research Products

• [Journal Article] Structures and functions of novel exopeptideses involved in peptide metabolism (2015)
  • Author(s): Sakamoto Y, Nonaka T
  • Journal Title: 生化学 Volume: 87 Issue: 6 Pages: 762-765
  • DOI: 10.14952/SEIKAGAKU.2015.870762
  • NAID: 40020687497
  • ISSN: 0037-1017
  • Year and Date: 2015-12-25
  • Peer Reviewed
• [Journal Article] Structural and mutational analyses of dipeptidyl peptidase 11 from Porphyromonas gingivalis reveal the molecular basis for strict substrate specificity. (2015)
  • Author(s): Sakamoto Y, Suzuki Y, Iizuka I, Tateoka C, Roppongi S, Fujimoto M, Inaka K, Tanaka H, Yamada M, Ohta K, Gouda H, Nonaka T, Ogasawara W, Tanaka N.
  • Journal Title: Scientific Reports Volume: 87 Issue: 1 Pages: 11151-11151
  • DOI: 10.1038/srep11151
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Crystallization and preliminary X-ray crystallographic studies of dipeptidyl peptidase 11 from Porphyromonas gingivalis. (2015)
  • Author(s): Sakamoto Y, Suzuki Y, Iizuka I, Tateoka C, Roppongi S, Fujimoto M, Gouda H, Nonaka T, Ogasawara W, Tanaka N.
  • Journal Title: Acta Crystallogr F Struct Biol Commun. Volume: 71 Issue: 2 Pages: 206-210
  • DOI: 10.1107/s2053230x15000424
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] S46 peptidases are the first exopeptidases to be members of clan PA. (2014)
  • Author(s): Sakamoto Y, Suzuki Y, Iizuka I, Tateoka C, Roppongi S, Fujimoto M, Inaka K, Tanaka H, Masaki M, Ohta K, Okada H, Nonaka T, Morikawa Y, Nakamura KT, Ogasawara W, Tanaka N.
  • Journal Title: Scientific Reports Volume: 4 Issue: 1 Pages: 4977-4977
  • DOI: 10.1038/srep04977
  • NAID: 120006832415
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Crystallization and preliminary X-ray crystallographic studies of dipeptidyl aminopeptidase BII from {\it Pseudoxanthomonas mexicana} WO24 (2014)
  • Author(s): Sakamoto, Y.
  • Journal Title: Acta Cryst. F Volume: 70 Issue: 2 Pages: 221-221
  • DOI: 10.1107/s2053230x13034584
  • Peer Reviewed
• [Journal Article] Identification of the catalytic triad of family S46 exopeptidases, closely related to clan PA endopeptidases. (2014)
  • Author(s): Suzuki, Y.
  • Journal Title: Scientific Reports Volume: 4 Issue: 1 Pages: 4292-4292
  • DOI: 10.1038/srep04292
  • Peer Reviewed
• [Presentation] 歯周病菌由来酸性アミノ酸特異的DPP（ジペプチジルペプチダーゼ）の構造生物学的研究（ (2016)
  • Author(s): 六本木沙織、鈴木義之、飯塚一平、舘岡千佳、藤本真友、伊中浩治、田仲広明、太田和敬、山田貢、合田浩明、野中孝昌、小笠原渉、田中信忠、阪本泰光
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-03-28
• [Presentation] 歯周病菌由来DPP11の構造生物学的研究 (2016)
  • Author(s): 六本木沙織、鈴木義之、飯塚一平、伊中浩治、田仲広明、太田和敬、山田貢、小笠原渉、田中信忠、野中孝昌、阪本泰光
  • Organizer: 2015 量子ビームサイエンスフェスタ
  • Place of Presentation: つくば市
  • Year and Date: 2016-03-15
• [Presentation] Structural and mutational studies of dipeptidyl peptidase 11 from Porphyromonas gingivalis (2015)
  • Author(s): 阪本泰光、鈴木義之、飯塚一平、舘岡千佳、六本木沙織、藤本真友、伊中浩治、田仲広明、太田和敬、山田貢、合田浩明、野中孝昌、小笠原渉、田中信忠
  • Organizer: 9th General Meeting of The International Proteolysis Society
  • Place of Presentation: ペナン、マレーシア
  • Year and Date: 2015-10-07
  • Int'l Joint Research
• [Presentation] First structure of Family S46 peptidase reveal exo-peptidase activity in Clan PA peptidases (2015)
  • Author(s): 飯塚一平、阪本泰光、鈴木義之、舘岡千佳、六本木沙織、藤本真友、伊中浩治、田仲広明、正木美佳、太田和敬、岡田宏文、野中孝昌、森川康、中村和郎、小笠原渉、田中信忠
  • Organizer: 9th General Meeting of The International Proteolysis Society
  • Place of Presentation: ペナン、マレーシア
  • Year and Date: 2015-10-05
• [Presentation] Clan PA S46ファミリーに属するDAP BIIの結晶構造解析 (2015)
  • Author(s): 飯塚一平、鈴木義之、館岡千佳、六本木沙織、藤本真友、伊中浩治、田仲広明、太田和敬、岡田宏文、野中孝昌、森川康、中村和郎、小笠原渉、田中信忠、阪本泰光
  • Organizer: 第54回日本薬学会東北支部大会
  • Place of Presentation: 矢巾町
  • Year and Date: 2015-09-26
• [Presentation] Pseudoxanthomonas mexicana WO24由来ジペプチジルアミノペプチダーゼの構造解析 (2015)
  • Author(s): 阪本泰光、鈴木義之、飯塚一平、館岡千佳、六本木沙織、藤本真友、伊中浩治、田中広明、太田和敬、岡田宏文、野中孝昌、森川康、中村和郎、小笠原渉、田中信忠
  • Organizer: 第135回日本薬学会年会
  • Place of Presentation: デザインクリエイティブセンター神戸（神戸）
  • Year and Date: 2015-03-28
• [Presentation] Clan PA に属するExopeptidase family S46 の構造機能相関の解明 (2015)
  • Author(s): 鈴木義之、阪本泰光、田中信忠、小笠原渉
  • Organizer: 日本農芸化学会2015年度年会
  • Place of Presentation: 岡山大学 津島キャンパス（岡山）
  • Year and Date: 2015-03-27
• [Presentation] Pseudoxanthomonas mexicana WO24 由来DAP BII の構造機能相関 (2015)
  • Author(s): 阪本泰光、鈴木義之、飯塚一平、館岡千佳、六本木沙織、藤本真友、伊中浩治、田中広明、太田和敬、岡田宏文、野中孝昌、森川康、中村和郎、小笠原渉、田中信忠
  • Organizer: 第3回物構研サイエンスフェスタ
  • Place of Presentation: エポカルつくば（つくば）
  • Year and Date: 2015-03-17
• [Presentation] Structural basis of exopeptidase activity of a dipeptidyl aminopeptidase BII, a member of the family S46 peptidases. (2014)
  • Author(s): Sakamoto Y, Suzuki Y, Iizuka I, Tateoka C, Roppongi S, Fujimoto M, Inaka K, Tanaka H, Masaki M, Ohta K, Okada H, Nonaka T, Morikawa Y, Nakamura KT, Ogasawara W, Tanaka N.
  • Organizer: 15th International Conference on the Crystallization of Biological Macromolecules.
  • Place of Presentation: ハンブルグ（ドイツ）
  • Year and Date: 2014-09-17
• [Presentation] Crystal Structure analyses of dipeptidyl aminopeptidase BII from P. mexicana WO24. (2014)
  • Author(s): Sakamoto Y, Suzuki Y, Iizuka I, Tateoka C, Roppongi S, Fujimoto M, Inaka K, Tanaka H, Masaki M, Ohta K, Okada H, Nonaka T, Morikawa Y, Nakamura KT, Ogasawara W, Tanaka N.
  • Organizer: The 23rd Congress and General Assembly of the International Union of Crystallography.
  • Place of Presentation: モントリオール（カナダ）
  • Year and Date: 2014-08-11
• [Presentation] Crystal structure analysis of dipeptidyl amino peptidase from P. mexicana WO24. (2014)
  • Author(s): Roppongi S, Tateoka C, Suzuki Y, Fujimoto M, Morisawa S, Iizuka I, Ogasawara W, Tanaka N, Sakamoto Y, Nonaka T.
  • Organizer: The 23rd Congress and General Assembly of the International Union of Crystallography.
  • Place of Presentation: モントリオール（カナダ）
  • Year and Date: 2014-08-09
• [Presentation] Crystal Structures of Dipeptidyl aminopeptidases from Pseudoxanthomonas mexicana WO24. (2014)
  • Author(s): Roppongi S, Suzuki Y, Iizuka I, Tateoka C, Fujimoto M, Inaka K, Tanaka H, Masaki M, Ohta K, Okada H, Morikawa Y, Nakamura KT, Ogasawara W, Tanaka N, Sakamoto Y, Nonaka T.
  • Organizer: New York Structural Biology Discussion Group Summer Meeting.
  • Place of Presentation: ニューヨーク（米国）
  • Year and Date: 2014-08-05
• [Presentation] Crystal structure studies of dipeptidyl aminopeptidase BII from Pseudoxanthomonas mexicana WO24. (2014)
  • Author(s): Sakamoto Y, Suzuki Y, Iizuka I, Tateoka C, Roppongi S, Fujimoto M, Inaka K, Tanaka H, Masaki M, Ohta K, Okada H, Nonaka T, Morikawa Y, Nakamura KT, Ogasawara W, Tanaka N.
  • Organizer: The 28th Symposium of the Protein Society
  • Place of Presentation: サンディエゴ（米国）
  • Year and Date: 2014-07-27
• [Presentation] 微小重力環境を利用したジペプチジルアミノペプチダーゼ結晶化 (2014)
  • Author(s): 阪本泰光
  • Organizer: 第14回日本蛋白質科学会年会
  • Place of Presentation: ワークピア横浜（横浜）
  • Year and Date: 2014-06-26
  • Invited
• [Presentation] Pseudoxanthomonas mexicana WO24 由来 dipeptidyl aminopeptidase 複合体の結晶構造 (2014)
  • Author(s): 六本木沙織、館岡千佳、森澤さおり、飯塚一平、藤本真友、鈴木義之、小笠原渉、田中信忠、阪本泰光、野中孝昌
  • Organizer: 第14回日本蛋白質科学会年会
  • Place of Presentation: 横浜産貿易ホール（横浜）
  • Year and Date: 2014-06-25
• [Remarks] JAXA プレスリリース DAP BII
  • URL: http://www.jaxa.jp/press/2014/05/20140516_dapbii_j.html
• [Remarks] 岩手医科大学 プレスリリース DAP BII
  • URL: http://www.iwate-med.ac.jp/news/n5-research/14051601-kikaku/
• [Remarks] 高エネルギー加速器研究機構 阪本泰光助教（岩手医科大）のPF実験が紹介
  • URL: http://www2.kek.jp/imss/news/2014/news.html
• [Remarks] ISS・きぼうマンスリーニュース第14号 JAXA PCG実験で成果
  • URL: http://iss.jaxa.jp/monthly/1405.php
• [Remarks] 科学技術振興機構 サイエンスチャンネル 薬が効かない！ 多剤耐性菌のナゾに迫る
  • URL: http://sciencechannel.jst.go.jp/M140001/detail/M140001006.html
• [Remarks] 国際宇宙ステーションでのタンパク質結晶生成実験結果から～
  • URL: http://www.jaxa.jp/press/2014/05/20140516_dapbii_j.html
• [Remarks] 世界で初めて、ファミリーS46ペプチダーゼに属する 酵素の立体構造および基質認識機構を解明
  • URL: http://www.iwate-med.ac.jp/news/n5-research/14051601-kikaku/