DB code: S00517

RLCP classification	1.13.30000.10 : Hydrolysis
CATH domain	3.40.50.1820 : Rossmann fold	Catalytic domain
E.C.	3.4.16.5
CSA
M-CSA
MACiE

CATH domain	Related DB codes (homologues)
3.40.50.1820 : 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	EC 3.4.16.5 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 deamidase lysosomal carboxypeptidase A phaseolin

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
E.C.
Compound	Peptide	H2O	Peptide	Peptidyl-tetrahedral intermediate	Acyl-enzyme	Tetrahedral intermediate
Type	peptide/protein	H2O	peptide/protein
ChEBI		15377 15377
PubChem		22247451 962 22247451 962

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
[3]	p.1253-1254

References
[1]
Resource
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
[2]
Resource
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
[3]
Resource
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
[4]
Resource
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
[5]
Resource
Comments
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
[6]
Resource
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

Comments
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.

Comments

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