DB code: S00408

RLCP classification 1.13.30000.39 : Hydrolysis
CATH domain 3.40.630.20 : Aminopeptidase Catalytic domain
E.C. 3.4.19.3
CSA 1aug
M-CSA 1aug
MACiE

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms MEROPS Pfam RefSeq
O07883 Pyrrolidone-carboxylate peptidase
EC 3.4.19.3
5-oxoprolyl-peptidase
Pyroglutamyl-peptidase I
PGP-I
C15.001 (Cysteine)
PF01470 (Peptidase_C15)
[Graphical View]
O73944 Pyrrolidone-carboxylate peptidase
EC 3.4.19.3
5-oxoprolyl-peptidase
Pyroglutamyl-peptidase I
PGP-I
Pyrase
C15.001 (Cysteine)
PF01470 (Peptidase_C15)
[Graphical View]
NP_579028.1 (Protein)
NC_003413.1 (DNA/RNA sequence)
P46107 Pyrrolidone-carboxylate peptidase
EC 3.4.19.3
5-oxoprolyl-peptidase
Pyroglutamyl-peptidase I
PGP-I
Pyrase
C15.001 (Cysteine)
PF01470 (Peptidase_C15)
[Graphical View]

KEGG enzyme name
pyroglutamyl-peptidase I
5-oxoprolyl-peptidase
pyrase
pyroglutamate aminopeptidase
pyroglutamyl aminopeptidase
L-pyroglutamyl peptide hydrolase
pyrrolidone-carboxyl peptidase
pyrrolidone-carboxylate peptidase
pyrrolidonyl peptidase
L-pyrrolidonecarboxylate peptidase
pyroglutamidase
pyrrolidonecarboxylyl peptidase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
O07883 PCP_THELI Release of an N-terminal pyroglutamyl group from a polypeptide, the second amino acid generally not being Pro. Homotetramer. Cytoplasm.
O73944 PCP_PYRFU Release of an N-terminal pyroglutamyl group from a polypeptide, the second amino acid generally not being Pro. Homotetramer made of two disulfide-linked dimers. Cytoplasm.
P46107 PCP_BACAM Release of an N-terminal pyroglutamyl group from a polypeptide, the second amino acid generally not being Pro. Homotetramer. Cytoplasm.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00017 C00012 C00001 C00017 C00012 I00153 I00154 I00155
E.C.
Compound Protein Peptide H2O Protein Peptide Peptidyl-Cys-tetrahedral-intermediate (with previous peptide) Acyl-enzyme(Peptidyl-Cys-acyl group) Peptidyl-Cys-tetrahedral-intermediate
Type peptide/protein peptide/protein H2O peptide/protein peptide/protein
ChEBI 15377
PubChem 22247451
962
1a2zA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1a2zB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1a2zC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1a2zD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1iofA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1iofB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1iofC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1iofD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ioiA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ioiB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ioiC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ioiD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1augA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1augB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1augC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1augD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P46107,PDB;1a2z

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1a2zA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 80;ARG 90;CYS 143;HIS 167 CYS 143
1a2zB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 80;ARG 90;CYS 143;HIS 167 CYS 143
1a2zC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 80;ARG 90;CYS 143;HIS 167 CYS 143
1a2zD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 80;ARG 90;CYS 143;HIS 167 CYS 143
1iofA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 79;ARG 89;CYS 142;HIS 166 CYS 142
1iofB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 79;ARG 89;CYS 142;HIS 166 CYS 142
1iofC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 79;ARG 89;CYS 142;HIS 166 CYS 142
1iofD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 79;ARG 89;CYS 142;HIS 166 CYS 142
1ioiA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 79;ARG 89; ;HIS 166 mutant C142S
1ioiB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 79;ARG 89; ;HIS 166 mutant C142S
1ioiC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 79;ARG 89; ;HIS 166 mutant C142S
1ioiD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 79;ARG 89; ;HIS 166 mutant C142S
1augA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 81;ARG 91;CYS 144;HIS 168 CYS 144
1augB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 291;ARG 301;CYS 354;HIS 378 CYS 354
1augC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 501;ARG 511;CYS 564;HIS 588 CYS 564
1augD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 711;ARG 721;CYS 774;HIS 798 CYS 774

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.240
[2]
p.405
[3]
p.111-112

References
[1]
Resource
Comments X-ray crystallography (1.73 Angstroms)
Medline ID
PubMed ID 10368293
Journal Structure Fold Des
Year 1999
Volume 7
Pages 237-44
Authors Singleton M, Isupov M, Littlechild J
Title X-ray structure of pyrrolidone carboxyl peptidase from the hyperthermophilic archaeon Thermococcus litoralis.
Related PDB 1a2z
Related UniProtKB
[2]
Resource
Comments X-ray crystallography (1.6 Angstroms)
Medline ID 99216536
PubMed ID 10196127
Journal Structure Fold Des
Year 1999
Volume 7
Pages 399-411
Authors Odagaki Y, Hayashi A, Okada K, Hirotsu K, Kabashima T, Ito K, Yoshimoto T, Tsuru D, Sato M, Clardy J
Title The crystal structure of pyroglutamyl peptidase I from Bacillus amyloliquefaciens reveals a new structure for a cysteine protease.
Related PDB 1aug
Related UniProtKB P46107
[3]
Resource
Comments X-ray crystallography (wildtype;2.2/mutant;2.7 Angstroms)
Medline ID
PubMed ID 11432786
Journal J Biochem (Tokyo)
Year 2001
Volume 130
Pages 107-18
Authors Tanaka H, Chinami M, Mizushima T, Ogasahara K, Ota M, Tsukihara T, Yutani K
Title X-ray crystalline structures of pyrrolidone carboxyl peptidase from a hyperthermophile, Pyrococcus furiosus, and its cys-free mutant.
Related PDB 1iof 1ioi
Related UniProtKB
[4]
Resource
Comments X-ray crystallography, Site-directed mutagenesis
Medline ID
PubMed ID 11359794
Journal J Biol Chem
Year 2001
Volume 276
Pages 18557-62
Authors Ito K, Inoue T, Takahashi T, Huang HS, Esumi T, Hatakeyama S, Tanaka N, Nakamura KT, Yoshimoto T
Title The mechanism of aubstrate eecognition of pyroglutamyl-peptidase I from Bacillus amyloliquefaciens as determined by X-ray crystallography and site-directed mutagenesis.
Related PDB
Related UniProtKB

Comments
The papers [1],[2] & [3] reported on the catalytic triad Cys-His-Glu, suggesting that this enzyme belongs to a cysteine protease family. However, the mutation of the catalytic nucleophilic residue, Cys, into Ser, retained the catalytic activity [1].
According to the literature [2], the oxyanion hole seems to be composed of the mainchain amide of Cys144(PDB;1aug) and sidechain of Arg91.

Created Updated
2002-09-27 2012-10-22