DB code: S00517

RLCP classification 1.13.30000.10 : Hydrolysis
CATH domain : Rossmann fold Catalytic domain

CATH domain Related DB codes (homologues) : Rossmann fold S00544 S00344 S00525 S00526 S00720 S00723 S00724 S00725 S00919 S00057 S00374 S00345 S00347 S00348 S00346 S00350 S00352 S00353 S00355 S00356 S00358 D00189 D00210 D00539 T00253

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Contains RefSeq MEROPS Pfam
P10619 Lysosomal protective protein
Cathepsin A
Carboxypeptidase C
Protective protein for beta-galactosidase
Lysosomal protective protein 32 kDa chain
Lysosomal protective protein 20 kDa chain
NP_000299.2 (Protein)
NM_000308.2 (DNA/RNA sequence)
NP_001121167.1 (Protein)
NM_001127695.1 (DNA/RNA sequence)
NP_001161066.1 (Protein)
NM_001167594.1 (DNA/RNA sequence)
S10.002 (Serine)
PF00450 (Peptidase_S10)
[Graphical View]

KEGG enzyme name
carboxypeptidase C
carboxypeptidase Y
serine carboxypeptidase I
cathepsin A
lysosomal protective protein
lysosomal carboxypeptidase A

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P10619 PPGB_HUMAN Release of a C-terminal amino acid with broad specificity. Heterodimer of a 32 kDa chain and a 20 kDa chain, disulfide-linked. Lysosome.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00012 C00001 C00012 I00087 I00085 I00086
Compound Peptide H2O Peptide Peptidyl-tetrahedral intermediate Acyl-enzyme Tetrahedral intermediate
Type peptide/protein H2O peptide/protein
ChEBI 15377
PubChem 22247451
1ivyA Unbound Unbound
1ivyB Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [3]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1ivyA SER 150;ASP 372;HIS 429 GLY 57;TYR 151
1ivyB SER 150;ASP 372;HIS 429 GLY 57;TYR 151

References for Catalytic Mechanism
References Sections No. of steps in catalysis

Comments variant galactosialidosis val-440
Medline ID 92097522
PubMed ID 1756715
Journal EMBO J
Year 1991
Volume 10
Pages 4041-8
Authors Zhou XY, Galjart NJ, Willemsen R, Gillemans N, Galjaard H, d'Azzo A
Title A mutation in a mild form of galactosialidosis impairs dimerization of the protective protein and renders it unstable.
Related PDB
Related UniProtKB P10619
Comments catalysis
Medline ID 91317848
PubMed ID 1907282
Journal J Biol Chem
Year 1991
Volume 266
Pages 14754-62
Authors Galjart NJ, Morreau H, Willemsen R, Gillemans N, Bonten EJ, d'Azzo A
Title Human lysosomal protective protein has cathepsin A-like activity distinct from its protective function
Related PDB
Related UniProtKB P10619
Comments X-ray crystallography (2.2 Angstroms)
Medline ID 96164441
PubMed ID 8591035
Journal Structure
Year 1995
Volume 3
Pages 1249-59
Authors Rudenko G, Bonten E, d'Azzo A, Hol WG
Title Three-dimensional structure of the human 'protective protein': structure of the precursor form suggests a complex activation mechanism.
Related PDB 1ivy
Related UniProtKB
Comments catalysis
Medline ID
PubMed ID 9435242
Journal Proc Natl Acad Sci U S A
Year 1998
Volume 95
Pages 621-5
Authors Rudenko G, Bonten E, Hol WG, d'Azzo A
Title The atomic model of the human protective protein/cathepsin A suggests a structural basis for galactosialidosis.
Related PDB
Related UniProtKB
Medline ID
PubMed ID 9878520
Journal Biochem Biophys Res Commun
Year 1998
Volume 253
Pages 228-34
Authors Itoh K, Naganawa Y, Kamei S, Shimmoto M, Sakuraba H
Title Stabilizing effect of lysosomal beta-galactosidase on the catalytic activity of protective protein/cathepsin A secreted by human platelets.
Related PDB
Related UniProtKB
Comments catalysis (mutation analysis)
Medline ID
PubMed ID 10944848
Journal J Hum Genet
Year 2000
Volume 45
Pages 200-6
Authors Takiguchi K, Itoh K, Shimmoto M, Ozand PT, Doi H, Sakuraba H
Title Structural and functional study of K453E mutant protective protein/cathepsin A causing the late infantile form of galactosialidosis.
Related PDB
Related UniProtKB

This enzyme belongs to the peptidase family S10.
According to the literature [3], this enzyme contains a catalytic triad, Ser150/Asp372/His429 (PDB; 1ivy), which is similar to those of trypsine-like serine peptidases. In this enzyme, Ser150 acts as a nucleophile, and His372 acts as Acid/Base. The negatively charged tetrahedral intermediate during catalysis is stablized by the oxyanion hole composed of the backbone amides.

Created Updated
2003-01-27 2011-02-16