- Email: [email protected]
X-Pro Dipeptidyl-Peptidase
757. X-Pro Dipeptidyl-Peptidase
[3] Fruhaufova´, L., Suska-Brezezinska, E., Barth, T., Rychlik, I. (1973). Rat liver enzyme inactivating oxytocin and its deamino-carba analogues. Coll. Czech. Chem. Commun. 38, 27932798. [4] Nardacci, N.J., Mukhopadhyay, S., Campbell, B.J. (1975). Partial purification and characterization of the antidiuretic hormone-inactivating enzyme from renal plasma membranes. Biochim. Biophys. Acta 377, 146157. [5] Campbell, B.J., Thysen, B., Chu, F.S. (1965). Peptidase catalyzed hydrolysis of antidiuretic hormone in toad bladder. Life Sci. 4, 21292140. [6] Glass, J.D., Schwartz, I.L., Walter, R. (1969). Enzymatic inactivation of peptide hormones possessing a C-terminal amide group. Proc. Natl. Acad. Sci. USA 63, 14261430.
3423
[7] Simmons, W.H., Walter, R. (1980). Carboxamidopeptidase: purification and characterization of a neurohypophyseal hormone inactivating peptidase from toad skin. Biochemistry 19, 3948. [8] Simmons, W.H., Walter, R. (1981). Enzyme inactivation of oxytocin: properties of carboxamidopeptidase, in: Neurohypophyseal Peptide Hormones and Other Biologically Active Peptides, Schlesinger, D.H., ed., New York: Elsevier North-Holland, pp. 151165. [9] Simmons, W.H. (1981). Carboxamidopeptidase: substrate specificity and similarity to cathepsin A. Fed. Proc. 40, 1440. [10] Rawlings, N.D., Barrett, A.J. (1994). Families of serine peptidases. Methods Enzymol. 244, 1961. [11] Remington, S.J., Breddam, K. (1994). Carboxypeptidases C and D. Methods Enzymol. 244, 231248.
William H. Simmons Department of Molecular and Cellular Biochemistry, Loyola University Chicago Stritch School of Medicine, 2160 S. First Avenue, Maywood, IL 60153, USA. Email: [email protected] This article is reproduced from the previous edition, Volume 2, pp. 19321934, r 2004, Elsevier Ltd., with revisions made by the Editors. © 2013 Elsevier Ltd. All rights reserved. DOI: http://dx.doi.org/10.1016/B978-0-12-382219-2.00756-0
Handbook of Proteolytic Enzymes, 3rd Edn ISBN: 978-0-12-382219-2
Chapter 757
X-Pro Dipeptidyl-Peptidase DATABANKS MEROPS name: Xaa-Pro Dipeptidyl-Peptidase MEROPS classification: clan SC, family S15, peptidase S15.001 IUBMB: EC 3.4.14.11 (BRENDA) Tertiary structure: Available Species distribution: class Bacilli Reference sequence from: Lactococcus lactis (UniProt: Q02W78)
sequenced simultaneously by Nardi et al. [11] and Mayo et al. [12], respectively. The genes from the lactobacilli were cloned by Meyer-Barton et al. [13], Vesanto et al. [10] and Yu¨ksel & Steele [14]. The pepX gene was named according to the standard terminology for peptidases from lactic acid bacteria [15], and accordingly, the enzyme is commonly known as PepX; it is also sometimes called PepXP.
Activity and Specificity Name and History The presence of X-Pro dipeptidyl-peptidase activity in intracellular extracts of 21 strains of lactobacilli and lactococci was first detected by Casey & Meyer [1] using Gly-Pro-NHMec as substrate. The enzyme, encoded by the pepX gene, was subsequently purified from several of these strains [210]. The pepX genes from Lactococcus lactis subsp. lactis and subsp. cremoris were cloned and
Dipeptides Xaa-Pro are cleaved from the N-termini of peptides [6,7], provided that the amino acids in the P2 and P10 positions are not Pro [7,9]. The enzyme also releases, though less efficiently, Xaa-Ala and Xaa-Gly dipeptides [5,7]. The optimal pH lies in the range 6.09.0 [210], and the optimal temperature is around 40 C [2,3,5,6,810]. PepX is a serine peptidase inhibited by DFP and PMSF. Some enzymes are inhibited by divalent cations such as Hg21 and Cu21 [2,810].
3424
757. X-Pro Dipeptidyl-Peptidase
Structural Chemistry
Distinguishing Features
The variants of PepX are generally dimeric enzymes [27] without disulfide bridges. The molecular mass of the monomer is 7290 kDa. One monomeric form [16] and one trimeric form [17] have been described. The pI of PepX is 4.54.7 [2,9]. The sequence surrounding the active-site serine was identified [18], and differs from the known consensus sequences of other serine peptidases (see Chapter 559). PepX from Lactococcus lactis has been crystallized [19] and its three-dimensional structure is resolved. PepX is a homodimeric enzyme with a two-fold symmetry axis [20]. Each monomer corresponds to a wide but thin molecule whose general shape is reminiscent of the map of Africa. It folds into four distinct, continuous domains. The α/β hydrolase fold (residues 163372 and 458548) is the largest and the catalytic one and contains the catalytic triad (Ser348, His468, Asp498). The shortest domain (residues 373457) is responsible for substrate binding specificity and is also involved in the dimerization. The N-terminus (residues 1 to 162) is mainly responsible for the dimerization. The C-terminus domain (215 residues) has no clear homology with a molecule deposited in the PDB.
No specific inhibitor is available for PepX. The catalytic activity is similar to that of dipeptidyl-peptidase IV (Chapter 749); the enzymes are both serine peptidases in clan SC, but differ enough in amino acid sequence to be placed in different families. As far as is known at present, PepX is confined to the lactic acid bacteria.
Preparation Strain variants of PepX have mainly been prepared from intracellular extracts of the lactic acid bacteria [2,4,510]. The PepXs from L. lactis subsp. lactis [19] and from Lactobacillus helveticus [10] were prepared as recombinant enzymes from E. coli.
Biological Aspects It has been shown that PepXs are able to hydrolyze sequentially peptides derived from β-casein, including β-casomorphin [6,7], and it is therefore believed that these enzymes play a role in the degradation of caseins. According to Atlan et al. [16] and Yu¨ksel & Steele [14], PepX is involved in the casein degradation pathway, providing essential amino acids to the lactobacilli. In contrast, Mayo et al. [21] have shown that PepX is not essential for the growth of lactococci in milk, but affects the peptide composition of fermented milk products. The same observation was made by Mierau et al. [22], who have studied the growth in milk of multiple-peptidase mutants of Lactococcus lactis. Thus, the roles of PepX in the proteolytic systems of lactobacilli and lactococci are probably different. PepX has been used for kinetically controlled peptide synthesis of proline-containing peptides [23,24].
References [1] Casey, M.G., Meyer, J. (1985). Presence of X-prolyl-dipeptidylpeptidase in lactic acid bacteria. J. Dairy Sci. 68, 32123215. [2] Meyer, J., Jordi, R. (1987). Purification and characterization of X-prolyl-dipeptidyl-aminopeptidase from Lactobacillus lactis and from Streptococcus thermophilus. J. Dairy Sci. 70, 738745. [3] Kiefer-Partsch, B., Bockelmann, W., Geis, A., Teuber, M. (1989). Purification of an X-prolyl-dipeptidyl aminopeptidase from Lactococcus lactis subsp. cremoris. Appl. Microbiol. Biotechnol. 31, 7578. [4] Booth, M., Fhaolain, I.N., Jennings, P.V., O’Cuinn, G. (1990). Purification and characterization of a post-proline dipeptidyl aminopeptidase from Streptococcus cremoris AM2. J. Dairy Res. 57, 8999. [5] Khalid, N.M., Marth, E.H. (1990). Purification and partial characterization of a prolyl-dipeptidyl-aminopeptidase from Lactobacillus helveticus CNRZ 32. Appl. Environ. Microbiol. 56, 381388. [6] Zevaco, C., Monnet, V., Gripon, J.-C. (1990). Intracellular X-prolyl dipeptidyl peptidase from Lactococcus lactis subsp. lactis: purification and properties. J. Appl. Bacteriol. 68, 357366. [7] Lloyd, R.J., Pritchard, G.G. (1991). Characterization of X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis subsp. lactis. J. Gen. Microbiol. 137, 4955. [8] Yan, T.-R., Lin, M.-Z., Lin, M.-J., Sun, B.J. (1991). Purification and characterization of an X-prolyl-dipeptidyl-aminopeptidase from Streptococcus cremoris nTR. J. Chinese Biochem. Soc. 20, 2132. [9] Habibi-Nafaji, M.B., Lee, B.H. (1994). Purification and characterization of X-prolyl-dipeptidyl-aminopeptidase from Lactobacillus casei subsp. casei LLG. Appl. Microbiol. Biotechnol. 42, 280286. [10] Vesanto, E., Savijoki, K., Rantanen, T., Steele, J.L., Palva, A. (1995). Molecular characterization, heterologous expression and purification of an X-prolyl-dipeptidyl aminopeptidase (pepX)gene from Lactobacillus helveticus. Microbiology 141, 30673075. [11] Nardi, M., Chopin, M.-C., Chopin, A., Cals, M.-M., Gripon, J.-C. (1991). Cloning and DNA sequence analysis of an X-prolyl dipeptidyl aminopeptidase gene from Lactococcus lactis subsp. lactis NCDO 763. Appl. Environ. Microbiol. 57, 4550. [12] Mayo, B., Kok, J., Venema, K., Bockelmann, W., Teuber, M., Reinke, H., Venema, G. (1991). Molecular cloning and sequence analysis of the X-prolyl dipeptidyl aminopeptidase gene from Lactococcus lactis subsp. cremoris. Appl. Environ. Microbiol. 57, 3844. [13] Meyer-Barton, E.C., Klein, J.R., Imam, M., Plapp, R. (1993). Cloning and sequence analysis of the X-prolyl-dipeptidyl-aminopeptidase gene (pepX) from Lactobacillus delbrueckii spp. lactis DSM7290. Appl. Microbiol. Biotechnol. 40, 8289.
757. X-Pro Dipeptidyl-Peptidase
¨ ., Steele, J.L. (1996). DNA sequence analysis, expres[14] Yu¨ksel, G.U sion, distribution and physiological role of the Xaa-prolyldipeptidyl aminopeptidase gene from Lactobacillus helveticus CNRZ32. Appl. Microbiol. Biotechnol. 44, 766773. [15] Tan, P.S.T., Poolman, B., Konings, W.N. (1993). Proteolytic enzymes of Lactococcus lactis. J. Dairy Res. 60, 269286. [16] Atlan, D., Laloi, P., Portalier, R. (1990). X-prolyl-dipeptidyl aminopeptidase of Lactobacillus delbrueckii subsp. bulgaricus: characterization of the enzyme and isolation of deficient mutants. Appl. Environ. Microbiol. 56, 21742179. [17] Miyakawa, H., Kobayashi, S., Shimamura, S., Tomita, M. (1991). Purification and characterization of an X-prolyl dipeptidyl aminopeptidase from Lactobacillus delbrueckii ssp. bulgaricus LBU-147. J. Dairy Sci. 74, 23752381. [18] Chich, J.-F., Chapot-Chartier, M.-P., Ribadeau-Dumas, B., Gripon, J.-C. (1992). Identification of the active site serine of the X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis. FEBS Lett. 314, 139142. [19] Chich, J.-F., Rigolet, P., Nardi, M., Gripon, J.-C., RibadeauDumas, L., Brunie, S. (1995). Purification, crystallization and preliminary X-ray analysis of PepX, an X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis. Proteins 23, 278281.
3425
[20] Rigolet, P., Me´chin, I., Delage, M.-M., Chich, J.-F. (2002). The structural basis for catalysis and specificity of the X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis. Structure 10(10), 13831394. [21] Mayo, B., Kok, J., Bockelmann, W., Haandrikman, A., Leenhouts, K.J., Venema, G. (1993). Effect of X-prolyl dipeptidyl aminopeptidase deficiency on Lactococcus lactis. Appl. Environ. Microbiol. 59, 20492055. [22] Mierau, I., Kunji, E.R.S., Leenhouts, K.J., Hellendorn, M.A., Haandrikman, A.J., Poolman, B., Konings, W.N., Venema, G., Kok, J. (1996). Multiple peptidase mutants of Lactococcus lactis are severely impaired in their ability to grow in milk. J. Bact. 178, 27942803. [23] Yoshpe-Besanc¸on, I., Gripon, J.-C., Ribadeau-Dumas, B. (1994). Xaa-Pro-dipeptidyl-aminopeptidase from Lactococcus lactis catalyses kinetically controlled synthesis of peptide bonds involving proline. Biotechnol. Appl. Biochem. 20, 131140. [24] Houbart, V., Ribadeau-Dumas, B., Chich, J.-F. (1995). Synthesis of enterostatin-amide by the Xaa-prolyl dipeptidyl aminopeptidase from Lactococcus lactis subsp. lactis NCDO 763. Biotechnol. Appl. Biochem. 21, 149159.
Jean-Franc¸ois Chich I.N.R.A., Laboratoire de Biochimie et Structure des Prote´ines, Unite´ Enzymologie, Domaine de Vilvert, 78352 Jouy-en-Josas Cedex, France. Email: [email protected] This article is reproduced from the previous edition, Volume 2, pp. 19341936, r 2004, Elsevier Ltd., with revisions made by the Editors. Handbook of Proteolytic Enzymes, 3rd Edn ISBN: 978-0-12-382219-2
© 2013 Elsevier Ltd. All rights reserved. DOI: http://dx.doi.org/10.1016/B978-0-12-382219-2.00757-2
[3] Fruhaufova´, L., Suska-Brezezinska, E., Barth, T., Rychlik, I. (1973). Rat liver enzyme inactivating oxytocin and its deamino-carba analogues. Coll. Czech. Chem. Commun. 38, 27932798. [4] Nardacci, N.J., Mukhopadhyay, S., Campbell, B.J. (1975). Partial purification and characterization of the antidiuretic hormone-inactivating enzyme from renal plasma membranes. Biochim. Biophys. Acta 377, 146157. [5] Campbell, B.J., Thysen, B., Chu, F.S. (1965). Peptidase catalyzed hydrolysis of antidiuretic hormone in toad bladder. Life Sci. 4, 21292140. [6] Glass, J.D., Schwartz, I.L., Walter, R. (1969). Enzymatic inactivation of peptide hormones possessing a C-terminal amide group. Proc. Natl. Acad. Sci. USA 63, 14261430.
3423
[7] Simmons, W.H., Walter, R. (1980). Carboxamidopeptidase: purification and characterization of a neurohypophyseal hormone inactivating peptidase from toad skin. Biochemistry 19, 3948. [8] Simmons, W.H., Walter, R. (1981). Enzyme inactivation of oxytocin: properties of carboxamidopeptidase, in: Neurohypophyseal Peptide Hormones and Other Biologically Active Peptides, Schlesinger, D.H., ed., New York: Elsevier North-Holland, pp. 151165. [9] Simmons, W.H. (1981). Carboxamidopeptidase: substrate specificity and similarity to cathepsin A. Fed. Proc. 40, 1440. [10] Rawlings, N.D., Barrett, A.J. (1994). Families of serine peptidases. Methods Enzymol. 244, 1961. [11] Remington, S.J., Breddam, K. (1994). Carboxypeptidases C and D. Methods Enzymol. 244, 231248.
William H. Simmons Department of Molecular and Cellular Biochemistry, Loyola University Chicago Stritch School of Medicine, 2160 S. First Avenue, Maywood, IL 60153, USA. Email: [email protected] This article is reproduced from the previous edition, Volume 2, pp. 19321934, r 2004, Elsevier Ltd., with revisions made by the Editors. © 2013 Elsevier Ltd. All rights reserved. DOI: http://dx.doi.org/10.1016/B978-0-12-382219-2.00756-0
Handbook of Proteolytic Enzymes, 3rd Edn ISBN: 978-0-12-382219-2
Chapter 757
X-Pro Dipeptidyl-Peptidase DATABANKS MEROPS name: Xaa-Pro Dipeptidyl-Peptidase MEROPS classification: clan SC, family S15, peptidase S15.001 IUBMB: EC 3.4.14.11 (BRENDA) Tertiary structure: Available Species distribution: class Bacilli Reference sequence from: Lactococcus lactis (UniProt: Q02W78)
sequenced simultaneously by Nardi et al. [11] and Mayo et al. [12], respectively. The genes from the lactobacilli were cloned by Meyer-Barton et al. [13], Vesanto et al. [10] and Yu¨ksel & Steele [14]. The pepX gene was named according to the standard terminology for peptidases from lactic acid bacteria [15], and accordingly, the enzyme is commonly known as PepX; it is also sometimes called PepXP.
Activity and Specificity Name and History The presence of X-Pro dipeptidyl-peptidase activity in intracellular extracts of 21 strains of lactobacilli and lactococci was first detected by Casey & Meyer [1] using Gly-Pro-NHMec as substrate. The enzyme, encoded by the pepX gene, was subsequently purified from several of these strains [210]. The pepX genes from Lactococcus lactis subsp. lactis and subsp. cremoris were cloned and
Dipeptides Xaa-Pro are cleaved from the N-termini of peptides [6,7], provided that the amino acids in the P2 and P10 positions are not Pro [7,9]. The enzyme also releases, though less efficiently, Xaa-Ala and Xaa-Gly dipeptides [5,7]. The optimal pH lies in the range 6.09.0 [210], and the optimal temperature is around 40 C [2,3,5,6,810]. PepX is a serine peptidase inhibited by DFP and PMSF. Some enzymes are inhibited by divalent cations such as Hg21 and Cu21 [2,810].
3424
757. X-Pro Dipeptidyl-Peptidase
Structural Chemistry
Distinguishing Features
The variants of PepX are generally dimeric enzymes [27] without disulfide bridges. The molecular mass of the monomer is 7290 kDa. One monomeric form [16] and one trimeric form [17] have been described. The pI of PepX is 4.54.7 [2,9]. The sequence surrounding the active-site serine was identified [18], and differs from the known consensus sequences of other serine peptidases (see Chapter 559). PepX from Lactococcus lactis has been crystallized [19] and its three-dimensional structure is resolved. PepX is a homodimeric enzyme with a two-fold symmetry axis [20]. Each monomer corresponds to a wide but thin molecule whose general shape is reminiscent of the map of Africa. It folds into four distinct, continuous domains. The α/β hydrolase fold (residues 163372 and 458548) is the largest and the catalytic one and contains the catalytic triad (Ser348, His468, Asp498). The shortest domain (residues 373457) is responsible for substrate binding specificity and is also involved in the dimerization. The N-terminus (residues 1 to 162) is mainly responsible for the dimerization. The C-terminus domain (215 residues) has no clear homology with a molecule deposited in the PDB.
No specific inhibitor is available for PepX. The catalytic activity is similar to that of dipeptidyl-peptidase IV (Chapter 749); the enzymes are both serine peptidases in clan SC, but differ enough in amino acid sequence to be placed in different families. As far as is known at present, PepX is confined to the lactic acid bacteria.
Preparation Strain variants of PepX have mainly been prepared from intracellular extracts of the lactic acid bacteria [2,4,510]. The PepXs from L. lactis subsp. lactis [19] and from Lactobacillus helveticus [10] were prepared as recombinant enzymes from E. coli.
Biological Aspects It has been shown that PepXs are able to hydrolyze sequentially peptides derived from β-casein, including β-casomorphin [6,7], and it is therefore believed that these enzymes play a role in the degradation of caseins. According to Atlan et al. [16] and Yu¨ksel & Steele [14], PepX is involved in the casein degradation pathway, providing essential amino acids to the lactobacilli. In contrast, Mayo et al. [21] have shown that PepX is not essential for the growth of lactococci in milk, but affects the peptide composition of fermented milk products. The same observation was made by Mierau et al. [22], who have studied the growth in milk of multiple-peptidase mutants of Lactococcus lactis. Thus, the roles of PepX in the proteolytic systems of lactobacilli and lactococci are probably different. PepX has been used for kinetically controlled peptide synthesis of proline-containing peptides [23,24].
References [1] Casey, M.G., Meyer, J. (1985). Presence of X-prolyl-dipeptidylpeptidase in lactic acid bacteria. J. Dairy Sci. 68, 32123215. [2] Meyer, J., Jordi, R. (1987). Purification and characterization of X-prolyl-dipeptidyl-aminopeptidase from Lactobacillus lactis and from Streptococcus thermophilus. J. Dairy Sci. 70, 738745. [3] Kiefer-Partsch, B., Bockelmann, W., Geis, A., Teuber, M. (1989). Purification of an X-prolyl-dipeptidyl aminopeptidase from Lactococcus lactis subsp. cremoris. Appl. Microbiol. Biotechnol. 31, 7578. [4] Booth, M., Fhaolain, I.N., Jennings, P.V., O’Cuinn, G. (1990). Purification and characterization of a post-proline dipeptidyl aminopeptidase from Streptococcus cremoris AM2. J. Dairy Res. 57, 8999. [5] Khalid, N.M., Marth, E.H. (1990). Purification and partial characterization of a prolyl-dipeptidyl-aminopeptidase from Lactobacillus helveticus CNRZ 32. Appl. Environ. Microbiol. 56, 381388. [6] Zevaco, C., Monnet, V., Gripon, J.-C. (1990). Intracellular X-prolyl dipeptidyl peptidase from Lactococcus lactis subsp. lactis: purification and properties. J. Appl. Bacteriol. 68, 357366. [7] Lloyd, R.J., Pritchard, G.G. (1991). Characterization of X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis subsp. lactis. J. Gen. Microbiol. 137, 4955. [8] Yan, T.-R., Lin, M.-Z., Lin, M.-J., Sun, B.J. (1991). Purification and characterization of an X-prolyl-dipeptidyl-aminopeptidase from Streptococcus cremoris nTR. J. Chinese Biochem. Soc. 20, 2132. [9] Habibi-Nafaji, M.B., Lee, B.H. (1994). Purification and characterization of X-prolyl-dipeptidyl-aminopeptidase from Lactobacillus casei subsp. casei LLG. Appl. Microbiol. Biotechnol. 42, 280286. [10] Vesanto, E., Savijoki, K., Rantanen, T., Steele, J.L., Palva, A. (1995). Molecular characterization, heterologous expression and purification of an X-prolyl-dipeptidyl aminopeptidase (pepX)gene from Lactobacillus helveticus. Microbiology 141, 30673075. [11] Nardi, M., Chopin, M.-C., Chopin, A., Cals, M.-M., Gripon, J.-C. (1991). Cloning and DNA sequence analysis of an X-prolyl dipeptidyl aminopeptidase gene from Lactococcus lactis subsp. lactis NCDO 763. Appl. Environ. Microbiol. 57, 4550. [12] Mayo, B., Kok, J., Venema, K., Bockelmann, W., Teuber, M., Reinke, H., Venema, G. (1991). Molecular cloning and sequence analysis of the X-prolyl dipeptidyl aminopeptidase gene from Lactococcus lactis subsp. cremoris. Appl. Environ. Microbiol. 57, 3844. [13] Meyer-Barton, E.C., Klein, J.R., Imam, M., Plapp, R. (1993). Cloning and sequence analysis of the X-prolyl-dipeptidyl-aminopeptidase gene (pepX) from Lactobacillus delbrueckii spp. lactis DSM7290. Appl. Microbiol. Biotechnol. 40, 8289.
757. X-Pro Dipeptidyl-Peptidase
¨ ., Steele, J.L. (1996). DNA sequence analysis, expres[14] Yu¨ksel, G.U sion, distribution and physiological role of the Xaa-prolyldipeptidyl aminopeptidase gene from Lactobacillus helveticus CNRZ32. Appl. Microbiol. Biotechnol. 44, 766773. [15] Tan, P.S.T., Poolman, B., Konings, W.N. (1993). Proteolytic enzymes of Lactococcus lactis. J. Dairy Res. 60, 269286. [16] Atlan, D., Laloi, P., Portalier, R. (1990). X-prolyl-dipeptidyl aminopeptidase of Lactobacillus delbrueckii subsp. bulgaricus: characterization of the enzyme and isolation of deficient mutants. Appl. Environ. Microbiol. 56, 21742179. [17] Miyakawa, H., Kobayashi, S., Shimamura, S., Tomita, M. (1991). Purification and characterization of an X-prolyl dipeptidyl aminopeptidase from Lactobacillus delbrueckii ssp. bulgaricus LBU-147. J. Dairy Sci. 74, 23752381. [18] Chich, J.-F., Chapot-Chartier, M.-P., Ribadeau-Dumas, B., Gripon, J.-C. (1992). Identification of the active site serine of the X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis. FEBS Lett. 314, 139142. [19] Chich, J.-F., Rigolet, P., Nardi, M., Gripon, J.-C., RibadeauDumas, L., Brunie, S. (1995). Purification, crystallization and preliminary X-ray analysis of PepX, an X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis. Proteins 23, 278281.
3425
[20] Rigolet, P., Me´chin, I., Delage, M.-M., Chich, J.-F. (2002). The structural basis for catalysis and specificity of the X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis. Structure 10(10), 13831394. [21] Mayo, B., Kok, J., Bockelmann, W., Haandrikman, A., Leenhouts, K.J., Venema, G. (1993). Effect of X-prolyl dipeptidyl aminopeptidase deficiency on Lactococcus lactis. Appl. Environ. Microbiol. 59, 20492055. [22] Mierau, I., Kunji, E.R.S., Leenhouts, K.J., Hellendorn, M.A., Haandrikman, A.J., Poolman, B., Konings, W.N., Venema, G., Kok, J. (1996). Multiple peptidase mutants of Lactococcus lactis are severely impaired in their ability to grow in milk. J. Bact. 178, 27942803. [23] Yoshpe-Besanc¸on, I., Gripon, J.-C., Ribadeau-Dumas, B. (1994). Xaa-Pro-dipeptidyl-aminopeptidase from Lactococcus lactis catalyses kinetically controlled synthesis of peptide bonds involving proline. Biotechnol. Appl. Biochem. 20, 131140. [24] Houbart, V., Ribadeau-Dumas, B., Chich, J.-F. (1995). Synthesis of enterostatin-amide by the Xaa-prolyl dipeptidyl aminopeptidase from Lactococcus lactis subsp. lactis NCDO 763. Biotechnol. Appl. Biochem. 21, 149159.
Jean-Franc¸ois Chich I.N.R.A., Laboratoire de Biochimie et Structure des Prote´ines, Unite´ Enzymologie, Domaine de Vilvert, 78352 Jouy-en-Josas Cedex, France. Email: [email protected] This article is reproduced from the previous edition, Volume 2, pp. 19341936, r 2004, Elsevier Ltd., with revisions made by the Editors. Handbook of Proteolytic Enzymes, 3rd Edn ISBN: 978-0-12-382219-2
© 2013 Elsevier Ltd. All rights reserved. DOI: http://dx.doi.org/10.1016/B978-0-12-382219-2.00757-2