EzCatDB: D00210

DB codeD00210
RLCP classification1.13.30000.13
CATH domainDomain 13.40.50.1820Catalytic domain
Domain 22.130.10.120
E.C.3.4.21.26
CSA1qfm

CATH domainRelated DB codes (homologues)
3.40.50.1820S00544,S00344,S00517,S00525,S00526,S00720,S00723,S00724,S00725,S00919,S00057,S00374,S00345,S00347,S00348,S00346,S00350,S00352,S00353,S00355,S00356,S00358,D00189,D00539,T00253

Enzyme Name
Swiss-protKEGG

P23687
Protein nameProlyl endopeptidaseprolyl oligopeptidase
post-proline cleaving enzyme
proline-specific endopeptidase
post-proline endopeptidase
proline endopeptidase
endoprolylpeptidase
prolyl endopeptidase
SynonymsPE
EC 3.4.21.26
Post-proline cleaving enzyme


Swiss-prot:Accession NumberP23687
Entry namePPCE_PIG
ActivityHydrolysis of Pro-|-Xaa >> Ala-|-Xaa in oligopeptides.
Subunit
Subcellular locationCytoplasm.
Cofactor


SubstratesProductsintermediates
KEGG-idC00001C00012C00746C00840C00012C00098I00087I00085I00086
CompoundH2OPeptideOxytocinVasopressinPeptideOligopeptidePeptidyl-tetrahedral intermediateAcyl-enzymeTetrahedral intermediate
TypeH2Opeptide/proteinamide group,amine group,aromatic ring (only carbon atom),disulfide bond,peptide/proteinamide group,amine group,aromatic ring (only carbon atom),carbohydrate,disulfide bond,lipid,peptide/proteinpeptide/proteinamine group,carboxyl group,peptide/protein


1e5tA01
UnboundUnboundUnboundUnboundUnboundUnboundUnboundIntermediate-analogue:GOL
1e8mA01
UnboundUnboundUnboundUnboundAnalogue:PHQ-GLY-PRO(chain I)UnboundUnboundUnbound
1e8nA01
Bound:GLY-PHE-GLY-PRO-PHE-GLY(chain I)UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1qfmA01
UnboundUnboundUnboundUnboundUnboundUnboundUnboundIntermediate-analogue:SGL
1qfsA01
UnboundUnboundUnboundUnboundUnboundUnboundUnboundIntermediate-analogue:ZPR
1e5tA02
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1e8mA02
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1e8nA02
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1qfmA02
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1qfsA02
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P23687 & literature [17], [22], [29], [32] & [33]
pdbCatalytic residuesMain-chain involved in catalysiscomment
1e5tA01TYR 473;SER 554;ASP 641;HIS 680
ASN 555

1e8mA01TYR 473;       ;ASP 641;HIS 680
ASN 555
mutant S554A
1e8nA01TYR 473;       ;ASP 641;HIS 680
ASN 555
mutant S554A
1qfmA01TYR 473;SER 554;ASP 641;HIS 680
ASN 555

1qfsA01TYR 473;SER 554;ASP 641;HIS 680
ASN 555

1e5tA02


1e8mA02


1e8nA02


1qfmA02


1qfsA02



References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[9]

[14]Scheme 1
[17]p.165
[22]

[29]p.354

references
[1]
CommentsACTIVE SITE HIS-680.
Medline ID91291146
PubMed ID2064618
JournalBiochem J
Year1991
Volume276
Pages837-40
AuthorsStone SR, Rennex D, Wikstrom P, Shaw E, Hofsteenge J
TitleInactivation of prolyl endopeptidase by a peptidylchloromethane. Kinetics of inactivation and identification of sites of modification.
Related Swiss-protP23687
[2]
PubMed ID1900195
JournalBiochemistry
Year1991
Volume30
Pages2195-203
AuthorsRennex D, Hemmings BA, Hofsteenge J, Stone SR
TitlecDNA cloning of porcine brain prolyl endopeptidase and identification of the active-site seryl residue.
[3]
PubMed ID2026166
JournalEur J Biochem
Year1991
Volume197
Pages441-7
AuthorsPolgar L
TitlepH-dependent mechanism in the catalysis of prolyl endopeptidase from pig muscle.
[4]
PubMed ID1590752
JournalBiochem J
Year1992
Volume283
Pages647-8
AuthorsPolgar L
TitleProlyl endopeptidase catalysis. A physical rather than a chemical step is rate-limiting.
[5]
PubMed ID1590775
JournalBiochem J
Year1992
Volume283
Pages871-6
AuthorsStone SR, Rennex D, Wikstrom P, Shaw E, Hofsteenge J
TitlePeptidyldiazomethanes. A novel mechanism of interaction with prolyl endopeptidase.
[6]
PubMed ID1510958
JournalBiochemistry
Year1992
Volume31
Pages7729-35
AuthorsPolgar L
TitleUnusual secondary specificity of prolyl oligopeptidase and the different reactivities of its two forms toward charged substrates.
[7]
PubMed ID1420194
JournalBiochemistry
Year1992
Volume31
Pages10769-73
AuthorsPolgar L, Patthy A
TitleCleavage of the Lys196-Ser197 bond of prolyl oligopeptidase: enhanced catalytic activity for one of the two active enzyme forms.
[8]
PubMed ID1569074
JournalJ Biol Chem
Year1992
Volume267
Pages8192-9
AuthorsChevallier S, Goeltz P, Thibault P, Banville D, Gagnon J
TitleCharacterization of a prolyl endopeptidase from Flavobacterium meningosepticum. Complete sequence and localization of the active-site serine.
[9]
PubMed ID8486154
JournalFEBS Lett
Year1993
Volume322
Pages227-30
AuthorsPolgar L, Kollt E, Hollosi M
TitleProlyl oligopeptidase catalysis. Reactions with thiono substrates reveal substrate-induced conformational change to be the rate-limiting step.
[10]
PubMed ID8027988
JournalJ Med Chem
Year1994
Volume37
Pages2071-8
AuthorsTanaka Y, Niwa S, Nishioka H, Yamanaka T, Torizuka M, Yoshinaga K, Kobayashi N, Ikeda Y, Arai H
TitleNew potent prolyl endopeptidase inhibitors: synthesis and structure-activity relationships of indan and tetralin derivatives and their analogues.
[11]
PubMed ID7932578
JournalJ Med Chem
Year1994
Volume37
Pages3492-502
AuthorsTsutsumi S, Okonogi T, Shibahara S, Ohuchi S, Hatsushiba E, Patchett AA, Christensen BG
TitleSynthesis and structure-activity relationships of peptidyl alpha-keto heterocycles as novel inhibitors of prolyl endopeptidase.
[12]
PubMed ID9148758
JournalBiochem J
Year1997
Volume322
Pages839-43
AuthorsKahyaoglu A, Haghjoo K, Kraicsovits F, Jordan F, Polgar L
TitleBenzyloxycarbonylprolylprolinal, a transition-state analogue for prolyl oligopeptidase, forms a tetrahedral adduct with catalytic serine, not a reactive cysteine.
[13]
PubMed ID9151967
JournalEur J Biochem
Year1997
Volume245
Pages381-5
AuthorsSchutkowski M, Jakob M, Landgraf G, Born I, Neubert K, Fischer G
TitleProbing substrate backbone function in prolyl oligopeptidase catalysis--large positional effects of peptide bond monothioxylation.
[14]
PubMed ID9325271
JournalJ Biol Chem
Year1997
Volume272
Pages25547-54
AuthorsKahyaoglu A, Haghjoo K, Guo F, Jordan F, Kettner C, Felfoldi F, Polgar L
TitleLow barrier hydrogen bond is absent in the catalytic triads in the ground state but Is present in a transition-state complex in the prolyl oligopeptidase family of serine proteases.
[15]
PubMed ID9128099
JournalJ Pept Res
Year1997
Volume49
Pages46-51
AuthorsNoula C, Kokotos G, Barth T, Tzougraki C
TitleNew fluorogenic substrates for the study of secondary specificity of prolyl oligopeptidase.
[16]
PubMed ID9839007
JournalBioorg Med Chem
Year1998
Volume6
Pages1775-80
AuthorsBordusa F, Jakubke HD
TitleThe specificity of prolyl endopeptidase from Flavobacterium meningoseptum: mapping the S' subsites by positional scanning via acyl transfer.
[17]
CommentsX-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS).
Medline ID98359116
PubMed ID9695945
JournalCell
Year1998
Volume94
Pages161-70
AuthorsFulop V, Bocskei Z, Polgar L
TitleProlyl oligopeptidase: an unusual beta-propeller domain regulates proteolysis.
Related PDB1qfm,1qfs
Related Swiss-protP23687
[18]
PubMed ID9427736
JournalEMBO J
Year1998
Volume17
Pages1-9
AuthorsMedrano FJ, Alonso J, Garcia JL, Romero A, Bode W, Gomis-Ruth FX
TitleStructure of proline iminopeptidase from Xanthomonas campestris pv. citri: a prototype for the prolyl oligopeptidase family.
[19]
PubMed ID9440697
JournalNature
Year1998
Volume391
Pages301-4
AuthorsQuemeneur E, Moutiez M, Charbonnier JB, Menez A
TitleEngineering cyclophilin into a proline-specific endopeptidase.
[20]
CommentsX-ray crystallography
PubMed ID11256612
JournalEMBO Rep
Year2000
Volume1
Pages277-81
AuthorsFulop V, Szeltner Z, Polgar L
TitleCatalysis of serine oligopeptidases is controlled by a gating filter mechanism.
Related PDB1e5t
[21]
PubMed ID10747969
JournalJ Biol Chem
Year2000
Volume275
Pages15000-5
AuthorsSzeltner Z, Renner V, Polgar L
TitleThe noncatalytic beta-propeller domain of prolyl oligopeptidase enhances the catalytic capability of the peptidase domain.
[22]
PubMed ID10716187
JournalProtein Sci
Year2000
Volume9
Pages353-60
AuthorsSzeltner Z, Renner V, Polgar L
TitleSubstrate- and pH-dependent contribution of oxyanion binding site to the catalysis of prolyl oligopeptidase, a paradigm of the serine oligopeptidase family.
[23]
PubMed ID11310664
JournalChem Pharm Bull (Tokyo)
Year2001
Volume49
Pages396-401
AuthorsFan W, Tezuka Y, Ni KM, Kadota S
TitleProlyl endopeptidase inhibitors from the underground part of Rhodiola sachalinensis.
[24]
CommentsX-ray crystallography
PubMed ID11031266
JournalJ Biol Chem
Year2001
Volume276
Pages1262-6
AuthorsFulop V, Szeltner Z, Renner V, Polgar L
TitleStructures of prolyl oligopeptidase substrate/inhibitor complexes. Use of inhibitor binding for titration of the catalytic histidine residue.
Related PDB1e8m,1e8n
[25]
PubMed ID11598112
JournalJ Biol Chem
Year2001
Volume276
Pages47078-86
AuthorsGrellier P, Vendeville S, Joyeau R, Bastos IM, Drobecq H, Frappier F, Teixeira AR, Schrevel J, Davioud-Charvet E, Sergheraert C, Santana JM
TitleTrypanosoma cruzi prolyl oligopeptidase Tc80 is involved in nonphagocytic mammalian cell invasion by trypomastigotes.
[26]
PubMed ID11278687
JournalJ Biol Chem
Year2001
Volume276
Pages19310-7
AuthorsHarris MN, Madura JD, Ming LJ, Harwood VJ
TitleKinetic and mechanistic studies of prolyl oligopeptidase from the hyperthermophile Pyrococcus furiosus.
[27]
PubMed ID12147298
JournalBiochem Pharmacol
Year2002
Volume64
Pages463-71
AuthorsVenalainen JI, Juvonen RO, Forsberg MM, Garcia-Horsman A, Poso A, Wallen EA, Gynther J, Mannisto PT
TitleSubstrate-dependent, non-hyperbolic kinetics of pig brain prolyl oligopeptidase and its tight binding inhibition by JTP-4819.
[28]
PubMed ID11983517
JournalBioorg Med Chem
Year2002
Volume10
Pages2199-206
AuthorsWallen EA, Christiaans JA, Saario SM, Forsberg MM, Venalainen JI, Paso HM, Mannisto PT, Gynther J
Title4-Phenylbutanoyl-2(S)-acylpyrrolidines and 4-phenylbutanoyl-L-prolyl-2(S)-acylpyrrolidines as prolyl oligopeptidase inhibitors.
[29]
PubMed ID11915948
JournalCell Mol Life Sci
Year2002
Volume59
Pages349-62
AuthorsPolgar L
TitleThe prolyl oligopeptidase family.
[30]
PubMed ID11964000
JournalChem Pharm Bull (Tokyo)
Year2002
Volume50
Pages515-8
AuthorsAnis I, Ahmed S, Malik A, Yasin A, Choudary MI
TitleEnzyme inhibitory constituents from Duranta repens.
[31]
PubMed ID12029050
JournalJ Bacteriol
Year2002
Volume184
Pages3329-37
AuthorsMorty RE, Fulop V, Andrews NW
TitleSubstrate recognition properties of oligopeptidase B from Salmonella enterica serovar Typhimurium.
[32]
PubMed ID12202494
JournalJ Biol Chem
Year2002
Volume277
Pages42613-22
AuthorsSzeltner Z, Rea D, Renner V, Fulop V, Polgar L
TitleElectrostatic effects and binding determinants in the catalysis of prolyl oligopeptidase. Site specific mutagenesis at the oxyanion binding site.
[33]
PubMed ID12228249
JournalJ Biol Chem
Year2002
Volume277
Pages44597-605
AuthorsSzeltner Z, Rea D, Juhasz T, Renner V, Mucsi Z, Orosz G, Fulop V, Polgar L
TitleSubstrate-dependent competency of the catalytic triad of prolyl oligopeptidase.
[34]
PubMed ID11809072
JournalJ Nat Prod
Year2002
Volume65
Pages76-8
AuthorsSong KS, Raskin I
TitleA prolyl endopeptidase-inhibiting benzofuran dimer from Polyozellus multiflex.
[35]
PubMed ID14514675
JournalJ Biol Chem
Year2003
Volume278
Pages48786-93
AuthorsSzeltner Z, Rea D, Renner V, Juliano L, Fulop V, Polgar L
TitleElectrostatic environment at the active site of prolyl oligopeptidase is highly influential during substrate binding.
[36]
PubMed ID15210359
JournalJ Mol Biol
Year2004
Volume340
Pages627-37
AuthorsSzeltner Z, Rea D, Juhasz T, Renner V, Fulop V, Polgar L
TitleConcerted structural changes in the peptidase and the propeller domains of prolyl oligopeptidase are required for substrate binding.

comments
This enzyme belongs to the peptidase family-S9A.
According to the literature [22] & [29], this enzyme has got a catalytic triad (Ser554, Asp641, His680) as in the classical serine proteases such as trypsin.
However, the oxyanion hole, which stabilizes the tetrahedral intermediate, is composed of the hydroxyl group of Tyr473 and mainchain amide group of Asn555 (see [29]).

createdupdated
2004-08-202011-02-18


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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