Genomes and Genes
pyroglutamyl peptidase i
Summary: An enzyme that catalyzes the release of a N-terminal pyroglutamyl group from a polypeptide provided the next residue is not proline. It is inhibited by thiol-blocking reagents and occurs in mammalian tissues, microorganisms, and plants. (From Enzyme Nomenclature, 1992) EC 18.104.22.168.
- Kabashima T, Li Y, Kanada N, Ito K, Yoshimoto T. Enhancement of the thermal stability of pyroglutamyl peptidase I by introduction of an intersubunit disulfide bond. Biochim Biophys Acta. 2001;1547:214-20 pubmed..However, the thermal stability of the S185C mutant was found to be 30 degrees C higher than that of wild-type. Thus the introduction of a disulfide bond enhanced thermal stability without changing the catalytic efficiency of the enzyme. ..
- Perez I, Blanco L, Sanz B, Errarte P, Ariz U, Beitia M, et al. Altered Activity and Expression of Cytosolic Peptidases in Colorectal Cancer. Int J Med Sci. 2015;12:458-67 pubmed publisher..Data suggest that cytosolic peptidases may be involved in colorectal carcinogenesis and point to the determination of this enzymes as a valuable method in the determination of CRC prognosis. ..
- Ramírez Expósito M, Garcia M, Mayas M, Ramirez M, Martinez Martos J. [Dietary cholesterol modifies pyroglutamyl aminopeptidase activity in mouse frontal cortex. Sexual differences]. Rev Neurol. 2001;32:904-7 pubmed..These increases may produce changes in TRH metabolism which may be related with alterations in its neuromodulatory functions and with the possible relationship between TRH and other neurotransmitter systems. ..
- Abe K, Saito F, Yamada M, Tokui T. Pyroglutamyl aminopeptidase I, as a drug metabolizing enzyme, recognizes xenobiotic substrates containing L-2-oxothiazolidine-4-carboxylic acid. Biol Pharm Bull. 2004;27:113-6 pubmed
- Charli J, Mendez M, Vargas M, Cisneros M, Assai M, Joseph Bravo P, et al. Pyroglutamyl peptidase II inhibition specifically increases recovery of TRH released from rat brain slices. Neuropeptides. 1989;14:191-6 pubmed..4.21.26). It weakly inhibited cytosolic pyroglutamyl peptidase I (EC 22.214.171.124)...
- Mozdzanowski J. Deblocking of proteins containing N-terminal pyroglutamic acid. Methods Mol Biol. 2003;211:365-9 pubmed
- Mucchetti G, Locci F, Massara P, Vitale R, Neviani E. Production of pyroglutamic acid by thermophilic lactic acid bacteria in hard-cooked mini-cheeses. J Dairy Sci. 2002;85:2489-96 pubmed..Under the experimental conditions applied, pGlu aminopeptidase activity was only detected in L. helveticus. Thus, pGlu formation in long-ripened cooked cheese may depend on the activity of thermophilic lactic acid bacteria. ..
- Panosian K, Edberg S. Measurement of constitutive L-pyrrolidonyl peptidase activity from Streptococcus and Enterococcus using tetrazotized 0-dianisidine. Antonie Van Leeuwenhoek. 1989;55:269-75 pubmed..This inexpensive reagent can be utilized either in a liquid form or dried on paper discs. ..
- Tappe D, Pukall R, Schumann P, Gronow S, Spiliotis M, Claus H, et al. Streptococcus merionis sp. nov., isolated from Mongolian jirds (Meriones unguiculatus). Int J Syst Evol Microbiol. 2009;59:766-70 pubmed publisher..nov. is proposed. The type strain is WUE3771(T) (=DSM 19192(T)=CCUG 54871(T)). ..
- Monsuur A, Stepniak D, Diosdado B, Wapenaar M, Mearin M, Koning F, et al. Genetic and functional analysis of pyroglutamyl-peptidase I in coeliac disease. Eur J Gastroenterol Hepatol. 2006;18:637-44 pubmed..We also determined the enzymatic activity of PGPEPI in duodenal biopsies. Our results uniformly indicate that PGPEP1 is not involved in the aetiology and pathology of CD. ..
- Mayas M, Ramírez Expósito M, García López M, Carrera M, Martínez Martos J. Chronic ethanol intake modifies pyrrolidon carboxypeptidase activity in mouse frontal cortex synaptosomes under resting and K+ -stimulated conditions: role of calcium. Neurosci Lett. 2008;439:75-8 pubmed publisher..Our data may also indicate that active peptides and their degrading peptidases are released together to the synaptic cleft to regulate the neurotransmitter/neuromodulator functions of these peptides, through a Ca2+ -dependent mechanism. ..
- Iimura S, Yagi H, Ogasahara K, Akutsu H, Noda Y, Segawa S, et al. Unusually slow denaturation and refolding processes of pyrrolidone carboxyl peptidase from a hyperthermophile are highly cooperative: real-time NMR studies. Biochemistry. 2004;43:11906-15 pubmed..The unusually slow refolding rate was discussed as originating in the conformations in the transition state and/or the retardation of reorganization in an ensemble of nonrandom denatured structures in the D(1) state. ..
- Dando P, Fortunato M, Strand G, Smith T, Barrett A. Pyroglutamyl-peptidase I: cloning, sequencing, and characterisation of the recombinant human enzyme. Protein Expr Purif. 2003;28:111-9 pubmed..Reversible inhibition was seen with 2-pyrrolidone (K(i)=50 microM), and surprisingly, with N-ethylmaleimide (K(i)=30 microM). ..
- Varona A, Blanco L, Lopez J, Gil J, Agirregoitia E, Irazusta J, et al. Altered levels of acid, basic, and neutral peptidase activity and expression in human clear cell renal cell carcinoma. Am J Physiol Renal Physiol. 2007;292:F780-8 pubmed..n = 223 UP/mg protein; P < 0.05). Soluble and particulate pyroglutamyl peptidase I activities, aminopeptidase A activity, and soluble aminopeptidase B activity do not vary in renal cancer...
- Tanaka H, Chinami M, Mizushima T, Ogasahara K, Ota M, Tsukihara T, et al. X-ray crystalline structures of pyrrolidone carboxyl peptidase from a hyperthermophile, Pyrococcus furiosus, and its cys-free mutant. J Biochem. 2001;130:107-18 pubmed
- Aguilar Valles A, Sanchez E, de Gortari P, García Vázquez A, Ramirez Amaya V, Bermudez Rattoni F, et al. The expression of TRH, its receptors and degrading enzyme is differentially modulated in the rat limbic system during training in the Morris water maze. Neurochem Int. 2007;50:404-17 pubmed..The differential modulation in anterior and posterior portions of the hippocampus is discussed. ..
- Ramirez M, Prieto I, Martinez J, Vargas F, Alba F. Renal aminopeptidase activities in animal models of hypertension. Regul Pept. 1997;72:155-9 pubmed..Our results suggest that AP activities play a role in the regulation of renal vasoactive peptides, and respond differently depending on the cause of hypertension. ..
- Marriq C, Lejeune P, Venot N, Vinet L. Hormone formation in the isolated fragment 1-171 of human thyroglobulin involves the couple tyrosine 5 and tyrosine 130. Mol Cell Endocrinol. 1991;81:155-64 pubmed
- Strydom D, Fett J, Lobb R, Alderman E, Bethune J, Riordan J, et al. Amino acid sequence of human tumor derived angiogenin. Biochemistry. 1985;24:5486-94 pubmed..Similarities are especially apparent around the major active-site residues His-12, Lys-41, and His-119 of ribonuclease which are conserved as are three of the four disulfide bonds.(ABSTRACT TRUNCATED AT 250 WORDS) ..
- Imada C. Enzyme inhibitors and other bioactive compounds from marine actinomycetes. Antonie Van Leeuwenhoek. 2005;87:59-63 pubmed..To our knowledge, this is the first report of actinomycetes from the marine environment that produce TTX. ..
- Carrera M, Ramírez Expósito M, Valenzuela M, Garcia M, Mayas M, Martinez Martos J. Serum pyrrolidone carboxypeptidase activity in N-methyl-nitrosourea induced rat breast cancer. Horm Metab Res. 2003;35:502-5 pubmed
- Higaki Sato N, Sato K, Esumi Y, Okumura T, Yoshikawa H, Tanaka Kuwajima C, et al. Isolation and identification of indigestible pyroglutamyl peptides in an enzymatic hydrolysate of wheat gluten prepared on an industrial scale. J Agric Food Chem. 2003;51:8-13 pubmed
- Ramírez Expósito M, Martinez Martos J, Mayas M, Tsuboyama G, Prieto I, Arechaga G, et al. [Aminoglycoside antibiotics neomycin and kanamycin inhibit the increase of of pyroglutamyl aminopeptidase activity by depolarizing synaptosomes of the frontal cortex of the rate]. Rev Neurol. 2000;30:1022-6 pubmed..A role for inositol 4,5-bisphosphate breakdown products is also suggested. ..
- Tan T, Ng S, He J. Microbiological characteristics, presumptive identification, and antibiotic susceptibilities of Staphylococcus lugdunensis. J Clin Microbiol. 2008;46:2393-5 pubmed publisher..The combination of positive responses to ornithine and pyrrolidonyl arylamidase identified all S. lugdunensis isolates. Resistance to penicillin and methicillin was detected in 27 and 5% of isolates, respectively. ..
- Ramirez M, Arechaga G, Martinez J, Prieto I, Ramírez Expósito M, Sanchez B, et al. Environmental light-darkness conditions induce changes in brain and peripheral pyroglutamyl-peptidase I activity. Neurochem Res. 2001;26:463-8 pubmed..These results support an influence of environmental light and darkness on pGluPI activity, which may reflect concomitant changes in its susceptible substrates and consequently in their functions. ..
- Kim J, Lee H, Lim J, Kim S, Cho S, Jeong W, et al. Molecular cloning and characterization of Mycobacterium bovis BCG pcp gene encoding pyrrolidone carboxyl peptidase. Mol Cells. 2001;12:347-52 pubmed..A multiple sequence alignment revealed highly conserved domains. The BCG pcp gene was overexpressed in Escherichia coli. The Pcp was purified to homogeneity. The recombinant protein was further confirmed by an enzymatic assay. ..
- Yamada M, Mori M. Thyrotropin-releasing hormone-degrading enzyme in human serum is classified as type II of pyroglutamyl aminopeptidase: influence of thyroid status. Proc Soc Exp Biol Med. 1990;194:346-51 pubmed..The present data indicate that a TRH-degrading enzyme in human serum possesses a nature identical to type II of pGlu-peptidase which is not altered by thyroid status. ..
- Alur H, Desai R, Mitra A, Johnston T. Inhibition of a model protease--pyroglutamate aminopeptidase by a natural oligosaccharide gum from Hakea gibbosa. Int J Pharm. 2001;212:171-6 pubmed
- Higaki Sato N, Sato K, Inoue N, Nawa Y, Kido Y, Nakabou Y, et al. Occurrence of the free and Peptide forms of pyroglutamic acid in plasma from the portal blood of rats that had ingested a wheat gluten hydrolysate containing pyroglutamyl peptides. J Agric Food Chem. 2006;54:6984-8 pubmed..The levels of free and peptide forms of pyroglutamic acid increased significantly and reached a maximum (approximately 40 nmol/mL) at 15 and 30 min after administration, respectively. ..
- Sokabe M, Kawamura T, Sakai N, Yao M, Watanabe N, Tanaka I. The X-ray crystal structure of pyrrolidone-carboxylate peptidase from hyperthermophilic archaea Pyrococcus horikoshii. J Struct Funct Genomics. 2002;2:145-54 pubmed..The result suggests that the thermostability of PhoPCP may be obtained by the accumulation of many weak factors...
- Duve H, Johnsen A, Scott A, Thorpe A. Allatostatins of the tiger prawn, Penaeus monodon (Crustacea: Penaeidea). Peptides. 2002;23:1039-51 pubmed
- Kaushik J, Ogasahara K, Yutani K. The unusually slow relaxation kinetics of the folding-unfolding of pyrrolidone carboxyl peptidase from a hyperthermophile, Pyrococcus furiosus. J Mol Biol. 2002;316:991-1003 pubmed
- Fowler E, Moyer M, Krishna R, Chin C, Wold F. Removal of N-terminal blocking groups from proteins. Curr Protoc Protein Sci. 2001;Chapter 11:Unit 11.7 pubmed publisher..Alternate protocols describe chemical removal of acetyl and longer-chain alkanoyl groups, as well as formyl groups to open the cyclic imide of pyrrolidone carboxylate. ..
- Crimmins D, McCourt D, Schwartz B. Facile analysis and purification of deblocked N-terminal pyroglutamyl peptides with a strong cation-exchange sulfoethyl aspartamide column. Biochem Biophys Res Commun. 1988;156:910-6 pubmed..In addition, the Sulfoethyl Aspartamide column was shown to be useful to monitor the extent of N-terminal glutamine cyclization formed during peptide purification and storage. ..
- Pedersen J, Lauritzen C, Madsen M, Weis Dahl S. Removal of N-terminal polyhistidine tags from recombinant proteins using engineered aminopeptidases. Protein Expr Purif. 1999;15:389-400 pubmed..The integrated process holds promises for use in large-scale production of pharmaceutical proteins because of a simple overall design, use of robust and inexpensive matrices, and use of enzymes of either recombinant or plant origin. ..
- Cummins P, O CONNOR B. Pyroglutamyl peptidase: an overview of the three known enzymatic forms. Biochim Biophys Acta. 1998;1429:1-17 pubmed..Pyroglutamyl peptidase activities isolated and characterized from bacterial sources are also reviewed and compared with their mammalian counterparts. ..
- Vagin A, Isupov M. Spherically averaged phased translation function and its application to the search for molecules and fragments in electron-density maps. Acta Crystallogr D Biol Crystallogr. 2001;57:1451-6 pubmed..The technique also allows superposition of distantly related macromolecules. The method has been implemented in a computer program MOLREP and successfully tested using experimental data sets. ..
- Tsunasawa S, Nakura S, Tanigawa T, Kato I. Pyrrolidone carboxyl peptidase from the hyperthermophilic Archaeon Pyrococcus furiosus: cloning and overexpression in Escherichia coli of the gene, and its application to protein sequence analysis. J Biochem. 1998;124:778-83 pubmed..in abstracts of the "International Congress on Exthermophiles '98" p. 58 (1998)]. To elucidate their contribution to the hyperthermostability of these enzymes, further structural studies are required...
- Awade A, Cleuziat P, Gonzales T, Robert Baudouy J. Characterization of the pcp gene encoding the pyrrolidone carboxyl peptidase of Bacillus subtilis. FEBS Lett. 1992;305:67-73 pubmed..The pcp gene has been over-expressed in E. coli, allowing the identification and partial characterization of Pcp protein. ..
- Flanagan T, Taylor L, Poulter L, Viveros O, Diliberto E. A novel 1745-dalton pyroglutamyl peptide derived from chromogranin B is in the bovine adrenomedullary chromaffin vesicle. Cell Mol Neurobiol. 1990;10:507-23 pubmed..3. A computer search through the Swiss-Prot protein sequence database revealed a 93% identity of BAM-1745 and a fragment of human chromogranin B (Gln580-Tyr593). ..
- Hellström J, Vehniäinen M, Mustonen M, Lövgren T, Lamminmaki U, Hellman J. Unfolding of the immunoglobulin light and heavy chains is required for the enzymatic removal of N-terminal pyroglutamyl residues. Biochim Biophys Acta. 2006;1764:1735-40 pubmed..Unfolding of the N-terminus would disrupt the immunoglobulin fold by breaking interactions between secondary structure elements and expose surfaces prone to aggregation. ..
- Kelly J, Scalabrino G, Slator G, Cullen A, Gilmer J, Lloyd D, et al. Structure-activity studies with high-affinity inhibitors of pyroglutamyl-peptidase II. Biochem J. 2005;389:569-76 pubmed..PPII inhibitors with this level of potency should find application in exploring the biological functions of TRH and PPII, and potentially provide a basis for development of novel therapeutics. ..
- Ito K, Inoue T, Takahashi T, Huang H, Esumi T, Hatakeyama S, et al. The mechanism of aubstrate eecognition of pyroglutamyl-peptidase I from Bacillus amyloliquefaciens as determined by X-ray crystallography and site-directed mutagenesis. J Biol Chem. 2001;276:18557-62 pubmed..In the pocket, Phe-10 is more important to the hydrophobic interaction than is Phe-142, and furthermore Phe-13 serves as an "induced fit" mechanism. ..
- Sandoval W, Pham V, Ingle E, Liu P, Lill J. Applications of microwave-assisted proteomics in biotechnology. Comb Chem High Throughput Screen. 2007;10:751-65 pubmed
- Brunetti L, Cacciatore I, Di Stefano A, Dupre S, Giorgi A, Luisi G, et al. Synthesis and biological evaluation of a novel pyroglutamyl-modified TRH analogue. Farmaco. 2002;57:479-86 pubmed..This peptide, which is significantly stabilized towards hydrolysis by pyroglutamyl peptidase type I (PP I, EC 126.96.36.199), has shown to maintain in vitro prolactin-releasing activity. ..
- Valdivia A, Irazusta J, Fernandez D, Múgica J, Ochoa C, Casis L. Pyroglutamyl peptidase I and prolyl endopeptidase in human semen: increased activity in necrozoospermia. Regul Pept. 2004;122:79-84 pubmed..In the present paper, we have characterized the activity of the TRH-degrading enzymes pyroglutamyl peptidase I and prolyl endopeptidase in the fluid and prostasomes of human semen and in subcellular fractions of the ..
- Sanchez B, Alba F, Luna J, Martinez J, Prieto I, Ramirez M. Pyroglutamyl peptidase I levels and their left-right distribution in the rat retina and hypothalamus are influenced by light-dark conditions. Brain Res. 1996;731:254-7 pubmedTo evaluate the effects of light and darkness on pyroglutamyl peptidase I activity (pGluPI) and its left-right distribution, pGluPI was measured bilaterally in the retina and hypothalamus under selected light-dark schedules...
- Schilling S, Hoffmann T, Wermann M, Heiser U, Wasternack C, Demuth H. Continuous spectrometric assays for glutaminyl cyclase activity. Anal Biochem. 2002;303:49-56 pubmed..This is the first report of a fast, continuous, and reliable determination of QC activity, even in the presence of ammonium ions, during the course of protein purification and enzymatic analysis. ..
- Ramírez Expósito M, Robert Baudouy J, Mayas M, Garcia M, Ramirez M, Martinez Martos J. Acetylcholinesterase inhibitor SDZ ENA 713 (Rivastigmine) increases brain pyrrolidone carboxyl peptidase activity. Eur Neuropsychopharmacol. 2001;11:381-3 pubmed
- Le Saux O, Robert Baudouy J. Pyroglutamic acid and iron regulate the expression of the pcp gene in Pseudomonas fluorescens MFO. FEMS Microbiol Lett. 1997;155:209-15 pubmed..pGlu and iron are therefore at least two of the transcriptional effectors of pcp expression. ..
- Suzuki Y, Motoi H, Sato K. Quantitative analysis of pyroglutamic acid in peptides. J Agric Food Chem. 1999;47:3248-51 pubmed..It cleaves more than 85% of pyroglutamate from peptides whose molecular weight ranges from 362.4 to 4599.4 Da. Thus, a new method is presented that quantitatively estimates N-terminal pyroglutamic acid residue in peptides. ..
- Werner W, Wu S, Mulkerrin M. The removal of pyroglutamic acid from monoclonal antibodies without denaturation of the protein chains. Anal Biochem. 2005;342:120-5 pubmed..All of the immunoglobulins digested with this method yielded heavy chain sequence, but the extent of deblocking was immunglobulin dependent (typically>50%). ..
- Thim L, Thomsen J, Christensen M, Jørgensen K. The amino acid sequence of pancreatic spasmolytic polypeptide. Biochim Biophys Acta. 1985;827:410-8 pubmed..The alignment of the sequences representing amino acids 14-49 and 63-98 shows pair-wise identical amino acid residues in 18 out of 36 positions, indicating that these two "domains" have been derived from a common gene. ..
- Mayas M, Martinez Martos J, Ramírez Expósito M, Garcia M, Tsuboyama G, Prieto I, et al. [In vitro study of the effect of ethanol on pyroglutamyl aminopeptidase activity in mouse synaptosomes under basal and stimulated conditions]. Rev Neurol. 2000;30:128-31 pubmed..These variations of pGluAP activity induced by ethanol, and their effects on their endogenous substrates, specially TRH, may be responsible for the behavioral changes associated to the alcoholism and mediated by TRH. ..
- Iimura S, Umezaki T, Takeuchi M, Mizuguchi M, Yagi H, Ogasahara K, et al. Characterization of the denatured structure of pyrrolidone carboxyl peptidase from a hyperthermophile under nondenaturing conditions: role of the C-terminal alpha-helix of the protein in folding and stability. Biochemistry. 2007;46:3664-72 pubmed..We can conclude that the native-like helix (alpha6-helix) of PCP-0SH is already constructed in the D1 state and is necessary for efficient refolding into the native structure and stabilization of PCP-0SH. ..
- Martinez J, Ramirez M, Prieto I, Alba F, Ramirez M. Influence of dietary supplementation with olive oil on pyroglutamyl-beta-naphthylamide hydrolysing activity in serum and different tissues of mice. Folia Biol (Praha). 1998;44:213-6 pubmed..The results may reflect functional modifications in susceptible endogenous substrates. ..
- Kilbane Z, Vaas P, Cuív P, O Connor B. Cloning and heterologous expression of bovine pyroglutamyl peptidase type-1 in Escherichia coli: purification, biochemical and kinetic characterisation. Mol Cell Biochem. 2007;297:189-97 pubmed..1, 141 and 652.17 microM, respectively. The lowest K (i), observed for Thyrotropin-releasing Hormone (TRH), indicates that rBtaPAP1(6H) has a higher affinity for tripeptides over dipeptides. ..
- Ko Y, Hullihen J, Hong S, Pedersen P. Mitochondrial F(0)F(1) ATP synthase. Subunit regions on the F1 motor shielded by F(0), Functional significance, and evidence for an involvement of the unique F(0) subunit F(6). J Biol Chem. 2000;275:32931-9 pubmed..The significance of the studies reported here, in relation to current views about ATP synthase structure and function in animal mitochondria, is discussed. ..
- Irazusta J, Gil J, Ruiz F, Agirregoitia N, Casis L, Silveira P. Effect of the disruption of body fluid balance on pyroglutamyl aminopeptidase (Type-1) in rat brain structures. Neuropeptides. 2002;36:333-40 pubmed..Although the deleterious or pro-homeostatic influence of this decay remains to be elucidated, the present data provide evidence for the involvement of this enzyme activity at this anatomical location in the water-electrolyte imbalance. ..
- Morty R, Bulau P, Pelle R, Wilk S, Abe K. Pyroglutamyl peptidase type I from Trypanosoma brucei: a new virulence factor from African trypanosomes that de-blocks regulatory peptides in the plasma of infected hosts. Biochem J. 2006;394:635-45 pubmed..The abnormal degradation of TRH and GnRH, and perhaps other neuropeptides N-terminally blocked with a pyroglutamyl moiety, by trypanosome PGP, may contribute to some of the endocrine lesions observed in African trypanosomiasis. ..
- Umezaki T, Iimura S, Noda Y, Segawa S, Yutani K. The confirmation of the denatured structure of pyrrolidone carboxyl peptidase under nondenaturing conditions: difference in helix propensity of two synthetic peptides with single amino acid substitution. Proteins. 2008;71:737-42 pubmed..The TFE-induced helical propensities for these peptide fragments confirmed the conclusions deduced from the H/D exchange data measured in the D(1) states of two proteins. ..
- Patti J, Schneider A, Garza N, Boles J. Isolation and characterization of pcp, a gene encoding a pyrrolidone carboxyl peptidase in Staphylococcus aureus. Gene. 1995;166:95-9 pubmed..However, the exact biological role of PYRases has yet to be elucidated. ..
- Cleuziat P, Awade A, Robert Baudouy J. Molecular characterization of pcp, the structural gene encoding the pyrrolidone carboxylyl peptidase from Streptococcus pyogenes. Mol Microbiol. 1992;6:2051-63 pubmed..pyogenes are discussed and compared with that from Bacillus subtilis. The lack of sequence identity with any other known protein or nucleotide sequence suggests that this enzyme belongs to a new class of peptidase. ..