• Yolanda Sanz


Lactic Acid Bacterium Dipeptidyl Peptidase Leucine Aminopeptidase Mammalian Enzyme Narrow Specificity 
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  1. Albiston, A.L., Ye, S. and Chai, S.Y. (2004) Membrane bound members of the M1 family: more than aminopeptidases. Protein Pept. Lett. 11, 491–500.PubMedCrossRefGoogle Scholar
  2. Ansorge, S., Bank, U., Nordhoff, K., Taeger, M. and Striggow, F. (2006) Dual alanyl aminopeptidase and dipeptidyl peptidase IV inhibitors for functionally influencing different cells and for treating immunological, inflammatory, neuronal and other diseases. Patent Application WO2005034940.Google Scholar
  3. Arfin, S.M., Kendall, R.L., Hal, L., Weaver, L.H., Stewart, A.E., Matthews, B.W. and Bradshaw, R.A. (1995) Eukaryotic methionyl aminopeptidases: two classes of cobalt-dependent enzymes. Proc. Natl. Acad. Sci. U S A. 92, 7714–7718.PubMedCrossRefADSGoogle Scholar
  4. Augustyns, K., Van der Veken, P., Senten, K. and Haemers, A. (2005) The therapeutic potential of inhibitors of dipeptidyl peptidase IV (DPP IV) and related proline-specific dipeptidyl aminopeptidases. Curr. Med. Chem. 12, 971–98.PubMedCrossRefGoogle Scholar
  5. Barret, A.J., Rawlings, N.D. and Woessner (eds) (2004) Handbook of proteolytic enzymes. Elsevier Academic Press. Oxford, UK.Google Scholar
  6. Bauvois, B. and Dauzonne, D. (2006) Aminopeptidase-N/CD13 (EC inhibitors: chemistry, biological evaluations, and therapeutic prospects. Med. Res. Rev. 26, 88–130.PubMedCrossRefGoogle Scholar
  7. Bazan, J.F., Weaver, L.H., Roderick, S.L., Huber, R. and Matthews, B.W. (1994) Sequence and structure comparison suggest that methionine aminopeptidase, prolidase, aminopeptidase P, and creatinase share a common fold. Proc. Natl. Acad. Sci. U S A. 91, 2473–2477.PubMedCrossRefADSGoogle Scholar
  8. Beninga, J., Rock, K.L. and Goldberg, A.L. (1998) Interferon-gamma can stimulate post-proteasomal trimming of the N terminus of an antigenic peptide by inducing leucine aminopeptidase. J. Biol. Chem. 273, 18734–18742.PubMedCrossRefGoogle Scholar
  9. Brown, N.J. (2005) Biological markers and diagnostic test for angiotensin converting enzyme inhibitor and vasopeptidase inhibitor-associated angioedema. Patent Application US6887679.Google Scholar
  10. Burley, S.K., David, P.R., Taylor, A. and Lipscomb, W.N. (1990) Molecular structure of leucine aminopeptidase at 2.7-A resolution. Proc. Natl. Acad. Sci. U S A. 87, 6878–6882.PubMedCrossRefADSGoogle Scholar
  11. Cappiello, M., Alterio, V., Amodeo, P., Del Corso, A., Scaloni. A., Pedone. C., Moschini, R., De Donatis, G.M., De Simone, G. and Mura, U. (2006) Metal ion substitution in the catalytic site greatly affects the binding of sulfhydryl-containing compounds to leucyl aminopeptidase. Biochem. 45, 3226–3234.CrossRefGoogle Scholar
  12. Chen, S., Vetro, J.A. and Chang, T.H. (2002) The specificity in vivo of two methionine aminopeptidases in Saccharomyces cerevisiae. Arch. Biochem. Biophys. 398, 87–93.PubMedCrossRefGoogle Scholar
  13. Chevalet, L., Souppe, J., De Leseleuc, J., Brunet, J. and Warmerdam, M.J. (2001) Aspergillus niger aminopeptidase compositions for making bread doughs and cheese. US6271013.Google Scholar
  14. Chich, J.F., Rigolet, P., Nardi. M., Gripon, J.C., Ribadeau-Dumas. B. and Brunie. S. (1995) Purification, crystallization, and preliminary X-ray analysis of PepX, an X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis. Proteins 23, 278–281.PubMedCrossRefGoogle Scholar
  15. Christensen, J.E., Dudley, E.G., Pederson, J.A. and Steel, J.L. (1999) Peptidases and amino acid catabolism in lactic acid bacteria. Antonie van Leeuwenhoek 76, 217–246.PubMedCrossRefGoogle Scholar
  16. Cogolludo, A., Perez-Vizcaino, F. and Tamargo, J. (2005) New insights in the pharmacological therapy of arterial hypertension. Curr. Opin. Nephrol. Hypertens. 14, 423–427.PubMedCrossRefGoogle Scholar
  17. Cottrell, G.S., Hooper, N.M. and Turner, A.J. (2000) Cloning, expression, and characterization of human cytosolic aminopeptidase P: a single manganese(II)-dependent enzyme. Biochemistry 39, 15121–15128.PubMedCrossRefGoogle Scholar
  18. Cunningham, D.F. and O’Connor, B. (1997) Proline specific peptidases. Biochim. Biophys. Acta 1343, 160–186.PubMedCrossRefGoogle Scholar
  19. Di Cagno, R., De Angelis, M., Auricchio, S., Greco, L., Clarke, C., De Vincenzi, M., Giovannini, C., D‘Archivio, M., Landolfo, F., Parrilli, G., Minervini, F., Arendt, E. and Gobbetti, M. (2004) Sourdough bread made from wheat and nontoxic flours and started with selected lactobacilli is tolerated in celiac sprue patients. Appl. Environ. Microbiol. 70, 1088–1096.PubMedCrossRefGoogle Scholar
  20. Engel, M., Hoffmann, T., Wagner, L., Wermann, M., Heiser, U., Kiefersauer, R., Huber, R., Bode, W., Demuth, H.U. and Brandstetter, H. (2003) The crystal structure of dipeptidyl peptidase IV (CD26) reveals its functional regulation and enzymatic mechanism. Proc. Natl. Acad. Sci. U S A. 100, 5063–5068.PubMedCrossRefADSGoogle Scholar
  21. Engel, C.K., Pirard, B., Schimanski, S., Kirsch, R., Habermann, J., Klingler, O., Schlotte, V., Weithmann, K.U. and Wendt K.U. (2005) Structural basis for the highly selective inhibition of MMP-13. Chem. Biol. 12, 181–189.PubMedCrossRefGoogle Scholar
  22. FitzGerald, R.J. and O’Cuinn, G. (2006) Enzymatic debittering of food protein hydrolysates. Biotechnol. Adv. 24, 234–237.PubMedCrossRefGoogle Scholar
  23. Fournie-Zaluski, M.C., Fassot, C., Valentin, B., Djordjijevic, D., Reaux-Le Goazigo, A., Corvol, P., Roques, B.P, and Llorens-Cortes, C. (2004) Brain renin-angiotensin system blockade by systemically active aminopeptidase A inhibitors: a potential treatment of salt-dependent hypertension. Proc. Natl. Acad. Sci. U S A. 101, 7775–7780.PubMedCrossRefADSGoogle Scholar
  24. Gilboa, R., Spungin-Bialik, A., Wohlfahrt, G., Schomburg, D., Blumberg, S. and Shoham, G. (2001) Interactions of Streptomyces griseus aminopeptidase with amino acid reaction products and their implications toward a catalytic mechanism. Proteins 44, 490–504.PubMedCrossRefGoogle Scholar
  25. Gonzales, T. and Robert-Baudouy, J. (1996) Bacterial aminopeptidases: properties and functions. FEMS Microbiol. 18, 319–344.CrossRefGoogle Scholar
  26. Hauser, F., Strassner, J. and Schaller, A. (2001) Cloning, expression, and characterization of tomato (Lycopersicon esculentum) aminopeptidase P. J. Biol. Chem. 276, 31732–31737.PubMedCrossRefGoogle Scholar
  27. Holz, R.C., Bzymek, K.P. and Swierczek, S.I. (2003) Co-catalytic metallopeptidases as pharmaceutical targets. Curr. Opin. Chem. Biol. 7, 197–206.PubMedCrossRefGoogle Scholar
  28. l‘Anson, K.J., Movahedi. S., Griffin. H.G., Gasson. M.J. and Mulholland, F. (1995) A non-essential glutamyl aminopeptidase is required for optimal growth of Lactococcus lactis MG1363 in milk. Microbiol. 141, 2873–2881.CrossRefGoogle Scholar
  29. Inguimbert, N., Coric, P., Dhotel, H., Bonnard, E., Llorens-Cortes, C., Mota, N., Fournie-Zaluski, M.C. and Roques, B.P. (2005) Synthesis and in vitro activities of new non-peptidic APA inhibitors. J. Pept. Res. 65, 175–188.PubMedCrossRefGoogle Scholar
  30. Jones, E.W. (1991) Three proteolytic systems in the yeast Saccharomyces cerevisiae. J. Biol. Chem. 266, 7963–7966.PubMedGoogle Scholar
  31. Joshua-Tor, L., Xu, H.E., Johnston, S.A. and Rees, D.C. (1995) Crystal structure of a conserved protease that binds DNA: the bleomycin hydrolase, Gal6. Science 269, 945–950.PubMedCrossRefADSGoogle Scholar
  32. Kim, H., Burley, S.K. and Lipscomb, W.N. (1993) Re-refinement of the X-ray crystal structure of bovine lens leucine aminopeptidase complexed with bestatin. J. Mol. Biol. 230, 722–724.PubMedCrossRefGoogle Scholar
  33. Kohno, H., Kanda, S. and Kanno, T. (1986) Immunoaffinity purification and characterization of leucine aminopeptidase from human liver. J. Biol. Chem. 261, 10744–10748.PubMedGoogle Scholar
  34. Kunji, E.R.S., Mierau, I., Hagting, A., Poolman, B. and Konings, W. N. (1996) The proteolytic systems of lactic acid bacteria. Antonie van Leeuwenhoek. 70, 187–221.PubMedCrossRefGoogle Scholar
  35. Leclerc, P.L., Gauthier, S.F., Bachelard, H., Santure, M. and Roy, D. (2001) Antihypertensive activity of casein-enriched milk fermented by Lactobacillus helveticus. Int. Dairy J. 12, 995–1004.CrossRefGoogle Scholar
  36. Leiting, B., Pryor, K.D., Wu, J.K., Marsilio, F., Patel, R.A., Craik, C.S., Ellman, J.A., Cummings, R.T. and Thornberry, N.A. (2003) Catalytic properties and inhibition of proline-specific dipeptidyl peptidases II, IV and VII. Biochem. J. 371, 525–532.PubMedCrossRefGoogle Scholar
  37. Linderstrom-Lang, K. (1929) Über Darmereosin [Concerning intestinal erepsin]. Z. Physiol. Chem. 182, 151–174.Google Scholar
  38. Lipscomb, W.N. and Sträter, N. (1996) Recent Advances in Zinc Enzymology. Chem. Rev. 96, 2375–2434.PubMedCrossRefGoogle Scholar
  39. Lowther, W.T. and Matthews, B.W. (2002) Metalloaminopeptidases: common functional themes in disparate structural surroundings. Chem. Rev. 102, 4581–4608.PubMedCrossRefGoogle Scholar
  40. McDonald, J.K. and Barret, A.J. (eds.) (1986) Mammalian proteases: a glossary and bibliography. Vol 2. Exopeptidases. Academic Press, London.Google Scholar
  41. Mata, L., Gripon, J.C. and Mistou, M.Y. (1999) Deletion of the four C-terminal residues of PepC converts an aminopeptidase into an oligopeptidase. Protein Eng. 12, 681–686.PubMedCrossRefGoogle Scholar
  42. Matsushima, M., Inoue, H., Ichinose, M., Tsukada, S., Miki, K., Kurokawa, K., Takahashi, T. and Takahashi, K. (1991) The nucleotide and deduced amino acid sequences of porcine liver proline-beta-naphthylamidase. Evidence for the identity with carboxylesterase. FEBS Lett. 293, 37–41.PubMedCrossRefGoogle Scholar
  43. Meisel, H. (2004) Multifunctional peptides encrypted in milk proteins. Biofactors 21, 55–61.PubMedCrossRefGoogle Scholar
  44. Mest, H.J. (2006) Dipeptidyl peptidase-IV inhibitors can restore glucose homeostasis in type 2 diabetics via incretin enhancement. Curr. Opin. Investig. Drugs 7, 338–343.PubMedGoogle Scholar
  45. Meyer-Barton, E., Klein, J.R., Henrich, B. and Plapp, R. (1994) X-prolyl-dipeptidyl peptidase from Lactobacillus delbrueckii ssp. lactis, nucleic acids coding for the same and its use in fermented foodstuffs preparation process. Patent Application WO9416082.Google Scholar
  46. Mistou, M.Y., Rigolet, P., Chapot-Chartier, M.P,, Nardi, M., Gripon, J.C, and Brunie, S. (1994) Crystallization and preliminary X-ray analysis of PepC, a thiol aminopeptidase from Lactoccocus lactis homologous to bleomycin hydrolase. J. Mol. Biol. 237, 160–162.PubMedCrossRefGoogle Scholar
  47. Nampoothiri, K.M., Nagy, V., Kovacs, K., Szakacs, G. and Pandey, A. (2005) l-leucine aminopeptidase production by filamentous Aspergillus fungi. Lett. Appl. Microbiol. 41, 498–504.PubMedCrossRefGoogle Scholar
  48. O‘Farrell, P.A., Gonzalez, F., Zheng, W., Johnston, S.A. and Joshua-Tor, L. (1999) Crystal structure of human bleomycin hydrolase, a self-compartmentalizing cysteine protease. Structure 7, 619–627.PubMedCrossRefGoogle Scholar
  49. Raksakulthai, R. and Haard, N.F. (2003) Exopeptidases and their application to reduce bitterness in food: a review. Crit. Rev. Food Sci. Nutr. 43, 401–445.PubMedCrossRefGoogle Scholar
  50. Rigolet, P., Xi, X.G., Rety, S. and Chich, J.F. (2005) The structural comparison of the bacterial PepX and human DPP-IV reveals sites for the design of inhibitors of PepX activity. FEBS J. 272, 2050–2059.PubMedCrossRefGoogle Scholar
  51. Roderick, S.L. and Matthews, B.W. (1993) Structure of the cobalt dependent methionine aminopeptidase from Escherichia coli: a new type of proteolytic enzyme. Biochem. 32, 3907–3912.CrossRefGoogle Scholar
  52. Ross, S., Giglione, C., Pierre, M., Espagne, C. and Meinnel, T. (2005) Functional and developmental impact of cytosolic protein N-terminal methionine excision in Arabidopsis. Plant Physiol. 137, 623–637.PubMedCrossRefGoogle Scholar
  53. Sanderink, G.J., Artur, Y. and Siest, G. (1988) Human aminopeptidases: a review of the literature. J. Clin. Chem. Biochem. 26, 795–807.Google Scholar
  54. Sanz, Y. and Toldrà, F. (1997) Purification and characterization of an aminopeptidase from Lactobacillus sakei . J. Agric. Food Chem. 45, 1552–1558.CrossRefGoogle Scholar
  55. Sanz, Y. and Toldrà, F. (2002) Purification and characterization of an arginine aminopeptidase from Lactobacillus sakei. Appl. Environ. Microbiol. 68, 1980–1987.PubMedCrossRefGoogle Scholar
  56. Sanz, Y., Sentandreu, M.A. and Toldrà, F. (2002) Role of muscle and bacterial peptidases in meat fermentation. In Research advances in the quality of meat and meat products. Toldrà F. (ed.). pp 143-155. Research Signpost, Trivandrum, ISBN: 81-7736-125-2, India.Google Scholar
  57. Savijoki, K., Ingmer. H. and Varmanen, P. (2006) Proteolytic systems of lactic acid bacteria. Appl. Microbiol. Biotechnol. April 21; [Epub ahead of print]Google Scholar
  58. Scharf, U., Stolz, P., Huscroft, S.C. and Schmidt-Hahn, K. (2006) Use of aminopeptidase in dough, doughs and bread improvers comprising aminopeptidase. Patent Application. WO2006009447.Google Scholar
  59. Schiffmann, R., Neugebauer, A. and Klein, C.D. (2006) Metal-mediated inhibition of Escherichia coli methionine aminopeptidase: structure-activity relationships and development of a novel scoring function for metal-ligand interactions. J. Med. Chem. 49, 511–522.PubMedCrossRefGoogle Scholar
  60. Scornik, O.A. and Botbol, V. (2001) Bestatin as an experimental tool in mammals. Curr. Drug Metab. 2, 67–85.PubMedCrossRefGoogle Scholar
  61. Selvakumar, P., Lakshmikuttyamma, A., Dimmock, J.R. and Sharma, R.K. (2005) Methionine aminopeptidase 2 and cancer. Biochim. Biophys. Acta 1765, 148–154.PubMedGoogle Scholar
  62. Seppo, L., Jauhiainen, T., Pousa, T. and Korpela, R. (2003) A fermented milk high in bioactive peptides has a blood pressure-lowering effect in hypertensive subjects. Am. J. Clin. Nutr. 77, 326–330.PubMedGoogle Scholar
  63. Shigeri, Y., Tsujimoto, Y., Yutaka, M. and Kunihiko, W. (2005) Method for producing degraded material of collagen. Patent Application. JP2005245285.Google Scholar
  64. Shimizu, T., Tani, K., Hase, K., Ogawa, H., Huang, L., Shinomiya, F. and Sone, S. (2002) CD13/aminopeptidase N-induced lymphocyte involvement in inflamed joints of patients with rheumatoid arthritis. Arthritis Rheum. 46, 2330–2338.PubMedCrossRefGoogle Scholar
  65. Sträter N. and Lipscomb, W.N. (1995) Two-metal ion mechanism of bovine lens leucine aminopeptidase: active site solvent structure and binding mode of L-leucinal, a gem-diolate transition state analogue, by X-ray crystallography. Biochem. 34, 14792–14800.CrossRefGoogle Scholar
  66. Sträter, N., Sherratt, D.J. and Colloms, S.D. (1999) X-ray structure of aminopeptidase A from Escherichia coli and a model for the nucleoprotein complex in Xer site-specific recombination. EMBO J. 18, 4513–4522.PubMedCrossRefGoogle Scholar
  67. Suchiibun, S.Y. K., Maikuru, A.M. and Daramu, B.B. (1993) Flavor reinforcing method for natural beef concentrated liquid. Patent Application EP 0505733.Google Scholar
  68. Tan, P.S.T., Poolman, B. and Konings, W.N. (1993) Proteolytic enzymes of Lactococcus lactis. J. Dairy Sci. 60, 269–286.Google Scholar
  69. Thunnissen, M.M.G.M., Nordlund, P. and Haeggström, J.Z. (2001) Crystal structure of human leukotriene A4 hydrolase, a bifunctional enzyme in inflammation. Nat. Struct. Biol. 8, 131–135.PubMedCrossRefGoogle Scholar
  70. Turner, A.J. (2004) Membrane alanyl aminopeptidase. In Handbook of proteolytic enzymes, Barret, A.J., Rawlings, N. D. and Woessner (eds), Vol 1 pp. 289–294. Elsevier Academic Press. Oxford, UK.Google Scholar
  71. Tu, C.J., Park, S-Y. and Walling, L.L. (2003) Isolation and characterization of the neutral leucine aminopeptidase (LapN) of tomato. Plant Physiol. 132, 243–255.PubMedCrossRefGoogle Scholar
  72. Yamauchi, Y., Ejiri, Y. and Tanaka, K. (2001) Purification of an aminopeptidase preferentially releasing N-terminal alanine from cucumber leaves and its identification as a plant aminopeptidase N. Biosci. Biotechnol. .Biochem. 65, 2802–2805.PubMedCrossRefGoogle Scholar
  73. Yaron, A. and Naider, F. (1993) Proline-dependent structural and biological properties of peptides and proteins. Crit. Rev. Biochem. Mol. Biol. 28, 31–81.PubMedCrossRefGoogle Scholar
  74. Yeh, J.R., Mohan, R. and Crews, C.M. (2000) The antiangiogenic agent TNP-470 requires p53 and p21CIP/WAF for endothelial cell growth arrest. Proc. Natl. Acad. Sci. U S A. 97, 12782–12787.PubMedCrossRefADSGoogle Scholar
  75. Yoshimoto, T., Orawski, A.T. and Simmons, W.H. (1994) Substrate specificity of aminopeptidase P from Escherichia coli: comparison with membrane-bound forms from rat and bovine lung. Arch. Biochem. Biophys. 311, 28–34.PubMedCrossRefGoogle Scholar
  76. Yoshimoto, T., Kabashima, T., Uchikawa, K., Inoue, T., Tanaka, N., Nakamura, K.T., Tsuru, M. and Ito, K. (1999) Crystal structure of prolyl aminopeptidase from Serratia marcescens. J. Biochem. (Tokyo) 126, 559–565.Google Scholar
  77. Zheng, W., Johnston, S.A. and Joshua-Tor, L. (1998) The unusual active site of Gal6/bleomycin hydrolase can act as a carboxypeptidase, aminopeptidase, and peptide ligase. Cell 93, 103–109.PubMedCrossRefGoogle Scholar
  78. Zhong, H. and Bowen, J.P. (2006) Antiangiogenesis drug design: multiple pathways targeting tumor vasculature. Curr. Med. Chem. 13, 849–862.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • Yolanda Sanz
    • 1
  1. 1.Departamento de Ciencia de los AlimentosInstituto de Agroquímica y Tecnología de Alimentos, CSICPaternaSpain

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