Biological Function of the M1 Family of Human Aminopeptidases

• Project/Area Number: 20590057
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Kyoto University
• Principal Investigator: HATTORI Akira Kyoto University, 薬学研究科, 准教授 (50300893)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: アミノペプチダーゼ / M1ファミリー / 抗原提示 / 阻害剤 / 部位特異的変異導入法 / 基質特異性 / 小胞体アミノペプチダーゼ / Laeverin / プロテアーゼ / 遺伝子発現調節

Research Abstract

Adipocyte-derived leucine aminopeptidase, leukocyte-derived arginine aminopeptidase and Laeverin are belonging to the M1 family of zinc-metallo aminopeptidases. In this study, biochemical and cell biological analyses were conducted to comprehend their catalytic mechanisms and characteristic subcellular localization/tissue distribution (endoplasmic reticulum retention or placenta specific expression). Several amino acid residues essential for catalysis were identified and genetic/cell biological tools (reporter plasmids and cell lines) were also established.

Research Products

• [Journal Article] The arabidopsis aminopeptidase LAP2 regulates plant growth (2011)
  • Author(s): Waditee R, Shibato J, Rakwal R, Sirisattha S, Hattori A, Nakano T, Takabe T, Tsujimoto M.
  • Journal Title: leaf longevity and stress response. New Phytologist in press
  • Peer Reviewed
• [Journal Article] Probing the S1 specificity pocket of the aminopeptidases that generate antigenic peptides. (2011)
  • Author(s): Zervoudi E, Papakyriakou A, Georgiadou D, Evnouchidou I, Gajda A, Poreba M, Salvesen GS, Drag M, Hattori A, Swevers L, Vourloumis D, Stratikos E.
  • Journal Title: Biochem J 435 Pages: 411-420
  • Peer Reviewed
• [Journal Article] Involvement of glutamine-238 in the substrate specificity of human laeverin/aminopeptidase Q. (2011)
  • Author(s): Goto Y, Yoshioka R, Arisaka N, Hattori A, Tsujimoto M.
  • Journal Title: Biol Pharm Bull 34 Pages: 24-27
  • NAID: 130000402257
  • Peer Reviewed
• [Journal Article] Involvement of glutamine-238 in the substrate specificity of human laeverin/aminopeptidase Q (2011)
  • Author(s): Goto Y., et al.
  • Journal Title: Biol.Pharm.Bull. Volume: 34 Pages: 24-27
  • Peer Reviewed
• [Journal Article] Probing the S1 specificity pocket of the aminopeptidases that generate antigenic peptides (2011)
  • Author(s): Zervoudi E., et al.
  • Journal Title: Biochemical J. Volume: 435 Pages: 411-420
  • Peer Reviewed
• [Journal Article] The Arabidopsis Aminopeptidase LAP2 Regulates Plant Growth, Leaf Longevity and Stress Response (2011)
  • Author(s): Waditee R., et al.
  • Journal Title: New Phytologist Volume: (in press)
  • Peer Reviewed
• [Journal Article] Histidine 379 of human laeverin/aminopeptidase Q, a nonconserved residue within the exopeptidase motif, defines its distinctive enzymatic properties. (2009)
  • Author(s): Maruyama M, Arisaka N, Goto Y, Ohsawa Y, Inoue H, Fujiwara H, Hattori A, Tsujimoto M.
  • Journal Title: J Biol Chem 284 Pages: 34692-34702
  • Peer Reviewed
• [Journal Article] The effect of recombinant aminopeptidase A (APA) on hypertension in pregnant spontaneously hypertensive rats (SHRs). (2009)
  • Author(s): Ishii M, Hattori A, Numaguchi Y, Ma X, Nagasaka T, Tsujimoto M, Murohara T, Kobayashi H, Mizutani S.
  • Journal Title: Early Hum Dev 85 Pages: 589-594
  • Peer Reviewed
• [Journal Article] Oxytocin hypersensitivity in pregnant P-LAP deficient mice. (2009)
  • Author(s): Ishii M, Naruse K, Hattori A, Tsujimoto M, Ishiura S, Numaguchi Y, Murohara T, Kobayashi H, Mizutani S.
  • Journal Title: Life Sci 84 Pages: 668-672
  • Peer Reviewed
• [Journal Article] Oxytocin hypersensitivity in pregnant P-LAP deficient mice (2009)
  • Author(s): Ishii M., et al.
  • Journal Title: Life Sci. 84 Pages: 668-672
  • Peer Reviewed
• [Journal Article] The effect of recombinant aminopeptidase A (APA) on hypertension in pregnant spontaneously hypertensive rats (SHRs) (2009)
  • Author(s): Ishii M., et al.
  • Journal Title: Earl. Hum. Dev. 85 Pages: 589-594
  • Peer Reviewed
• [Journal Article] Histidine-379 of human Laeverin/aminopeptidase Q, a non-conserved residue within the exopeptidase motif, defines its distinctive enzymatic properites (2009)
  • Author(s): Maruyama M., et al.
  • Journal Title: J. Biol. Chem. 284 Pages: 34692-34702
  • Peer Reviewed
• [Journal Article] Oxytocin hypersensitivity in pregnant P-LAP deficient mice. (2009)
  • Author(s): Ishii M., et al.
  • Journal Title: Life Sci. (in press)
  • Peer Reviewed
• [Journal Article] Glutamine-181 is crucial in the enzymatic activity and substrate specificity of human endoplasmic-reticulum aminopeptidase-1. (2008)
  • Author(s): Goto Y, Tanji H, Hattori A, Tsujimoto M.
  • Journal Title: Biochem J 416 Pages: 109-116
  • Peer Reviewed
• [Journal Article] The effect of recombinant aminopeptidase a on hypertension in spontaneously hypertensive rats: its effect in comparison with candesartan. (2008)
  • Author(s): Ishii M, Hattori A, Numaguchi Y, Tsujimoto M, Ishiura S, Kobayashi H, Murohara T, Wright JW, Mizutani S.
  • Journal Title: Horm Metab Res 40 Pages: 887-891
  • Peer Reviewed
• [Journal Article] New insights into the importance of aminopeptidase A in hypertension. (2008)
  • Author(s): Mizutani S, Ishii M, Hattori A, Nomura S, Numaguchi Y, Tsujimoto M, Kobayshi H, Murohara T, Wright JW.
  • Journal Title: Heart Fail Rev 13 Pages: 273-284
  • Peer Reviewed
• [Journal Article] Biochemical and enzymatic properties of the M1 family of aminopeptidases involved in the regulation of blood pressure. (2008)
  • Author(s): Tsujimoto M, Goto Y, Maruyama M, Hattori A.
  • Journal Title: Heart Fail Rev 13 Pages: 285-29
  • Peer Reviewed
• [Journal Article] The effect of recombinant aminopeptidase A on hypertension in spontaneously hypertensive rats : its effect in comparison with candesartan. (2008)
  • Author(s): Ishii M., et al.
  • Journal Title: Horm. Metab. Res. 40 Pages: 887-891
  • Peer Reviewed
• [Journal Article] Glutamine-181 is crucial in the enzymatic activity and substrate specificity of human endoplasmic-reticulum aminopeptidase-1. (2008)
  • Author(s): Goto Y., et al.
  • Journal Title: Biochem. J. 416 Pages: 109-116
  • Peer Reviewed
• [Journal Article] Biochemical and enzymatic properties of the Ml family of aminopeptidases involved in the regulation of blood pressure. (2008)
  • Author(s): Tsujimoto M., et al.
  • Journal Title: Heart Fail. Rev. 13 Pages: 285-289
  • Peer Reviewed
• [Journal Article] New insights into the importance of aminopeptidase A in hypertension. (2008)
  • Author(s): Mizutani S., et al.
  • Journal Title: Heart Fail. Rev. 13 Pages: 273-284
  • Peer Reviewed
• [Presentation] Phagocytosis of macrophages is facilitated by secreted ER-aminopeptidase 1. (2010)
  • Author(s): 後藤芳邦、小川健司、服部明、辻本雅文
  • Organizer: 第33回日本分子生物学会・第83回日本生化学会合同年会
  • Place of Presentation: 兵庫・神戸
  • Year and Date: 2010-12-10
• [Presentation] Phagocytosis of macrophages is facilitated by secreted ER-aminopeptidase 1 (2010)
  • Author(s): 後藤芳邦
  • Organizer: 第33回日本分子生物学会・第83回日本生化学会合同年会
  • Place of Presentation: 兵庫・神戸ポートアイランド
  • Year and Date: 2010-12-10
• [Presentation] Histidine-379 of human laeverin/aminopeptidase Q, a non-conserved residue within the exopeptidase motif, defines its distinctive enzymatic properties (2009)
  • Author(s): Hattori A, Maruyama M, Arisaka Y, Goto Y, Ohsawa Y, Inoue H, Fujiwara H, Tsujimoto M
  • Organizer: 6th General meeting of the International Proteolytic Society
  • Place of Presentation: Gold Coast, Australia.
  • Year and Date: 2009-10-27
• [Presentation] ERAP-1/A-LAP is secreted from macrophages treated with IFN- and LPS (2009)
  • Author(s): Goto Y, Hattori A, Tsujimoto M
  • Organizer: 6th General meeting of the International Proteolytic Society.
  • Place of Presentation: Gold Coast, Australia
  • Year and Date: 2009-10-27
• [Presentation] Histidine-379 of human Laeverin/aminopeptidase Q, a non-conserved residue within the exopeptidase motif, defines its distincitive enzymatic properites (2009)
  • Author(s): Hattori A, et al.
  • Organizer: 6th General Meeting of the International Proteolysis Society
  • Place of Presentation: Gold Coast, Australia
  • Year and Date: 2009-10-27
• [Presentation] マクロファージにおけるカルシウムを介した小胞体アミノペプチダーゼ-1の分泌 (2009)
  • Author(s): 後藤芳邦、服部明、辻本雅文
  • Organizer: 第82回日本生化学会
  • Place of Presentation: 兵庫・神戸
  • Year and Date: 2009-10-23
• [Presentation] 小胞体アミノペプチダーゼの基質認識機構 (2009)
  • Author(s): 後藤芳邦、服部明、辻本雅文
  • Organizer: 第129回日本薬学会年会
  • Place of Presentation: 京都・京都
  • Year and Date: 2009-03-26
• [Presentation] 小胞体アミノペプチダーゼの基質認識機構 (2009)
  • Author(s): 辻本雅文
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都府京都市
  • Year and Date: 2009-03-26
• [Presentation] 点変異導入によるヒトLaeverinのHis379残基の機能解析 (2008)
  • Author(s): 有坂尚美、丸山正人、服部明、辻本雅文
  • Organizer: 第31回日本分子生物学会・第82回日本生化学会合同年会
  • Place of Presentation: 兵庫・神戸
  • Year and Date: 2008-12-10
• [Presentation] ヒト脂肪細胞由来ロイシンアミノペプチダーゼのGln-181残基は基質特異性に重要である (2008)
  • Author(s): 後藤芳邦、丹治弘江、服部明、辻本雅文
  • Organizer: 第31回日本分子生物学会・第81回日本生化学会合同年会
  • Place of Presentation: 兵庫・神戸
  • Year and Date: 2008-12-10
• [Presentation] 点変異導入によるヒトLaeverinのHis379残基の機能解析 (2008)
  • Author(s): 有坂尚美
  • Organizer: 第31回日本分子生物学会年会/第81回日本生化学会大会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2008-12-10
• [Presentation] ヒト脂肪細胞由来ロイシンアミノペプチダーゼのGln-181は基質特異性に重要である (2008)
  • Author(s): 後藤芳邦
  • Organizer: 第31回日本分子生物学会年会/第81回日本生化学会大会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2008-12-10
• [Presentation] ヒトLaeverinの酵素学的性状の発現におけるHis379残基の役割 (2008)
  • Author(s): 有坂尚美、丸山正人、服部明、辻本雅文
  • Organizer: 第13回病態と治療のおけるプロテアーゼとインヒビター学会
  • Place of Presentation: 大阪・千里
  • Year and Date: 2008-08-22
• [Presentation] ヒト脂肪細胞由来ロイシンアミノペプチダーゼのGln-181残基は基質特異性に重要である (2008)
  • Author(s): 後藤芳邦、丹治弘江、服部明、辻本雅文
  • Organizer: 第13回病態と治療のおけるプロテアーゼとインヒビター学会
  • Place of Presentation: 大阪・千里
  • Year and Date: 2008-08-22
• [Presentation] ヒトLaeverinの酵素学的性状の発現におけるHis379残基の役割 (2008)
  • Author(s): 有坂尚美
  • Organizer: 第13回病態と治療におけるプロテアーゼとインヒビター学会
  • Place of Presentation: 大阪府豊中市
  • Year and Date: 2008-08-22
• [Book] Handbook of Proteolytic Enzymes, 3rd Edition (2011)
  • Author(s): Hattori A., et al.
  • Publisher: Elsevier(in press)