EzCatDB: S00517
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DB codeS00517
RLCP classification1.13.30000.10 : Hydrolysis
CATH domainDomain 13.40.50.1820 : Rossmann foldCatalytic domain
E.C.3.4.16.5

CATH domainRelated DB codes (homologues)
3.40.50.1820 : Rossmann foldS00544,S00344,S00525,S00526,S00720,S00723,S00724,S00725,S00919,S00057,S00374,S00345,S00347,S00348,S00346,S00350,S00352,S00353,S00355,S00356,S00358,D00189,D00210,D00539,T00253

Enzyme Name
UniProtKBKEGG

P10619
Protein nameLysosomal protective proteincarboxypeptidase C
carboxypeptidase Y
serine carboxypeptidase I
cathepsin A
lysosomal protective protein
deamidase
lysosomal carboxypeptidase A
phaseolin
SynonymsEC 3.4.16.5
Cathepsin A
Carboxypeptidase C
Protective protein for beta-galactosidase
ContainsLysosomal protective protein 32 kDa chain
Lysosomal protective protein 20 kDa chain
RefSeqNP_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)
MEROPSS10.002 (Serine)
PfamPF00450 (Peptidase_S10)
[Graphical view]


UniProtKB:Accession NumberP10619
Entry namePPGB_HUMAN
ActivityRelease of a C-terminal amino acid with broad specificity.
SubunitHeterodimer of a 32 kDa chain and a 20 kDa chain, disulfide-linked.
Subcellular locationLysosome.
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC00012C00001C00012I00087I00085I00086
CompoundPeptideH2OPeptidePeptidyl-tetrahedral intermediateAcyl-enzymeTetrahedral intermediate
Typepeptide/proteinH2Opeptide/protein


ChEBI
15377




PubChem
962
22247451




              
1ivyAUnbound Unbound   
1ivyBUnbound Unbound   

Active-site residues
resource
literature [3]
pdbCatalytic residuesMain-chain involved in catalysis
          
1ivyASER 150;ASP 372;HIS 429
GLY 57;TYR 151
1ivyBSER 150;ASP 372;HIS 429
GLY 57;TYR 151

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[3]p.1253-1254

references
[1]
Commentsvariant galactosialidosis val-440
Medline ID92097522
PubMed ID1756715
JournalEMBO J
Year1991
Volume10
Pages4041-8
AuthorsZhou XY, Galjart NJ, Willemsen R, Gillemans N, Galjaard H, d'Azzo A
TitleA mutation in a mild form of galactosialidosis impairs dimerization of the protective protein and renders it unstable.
Related UniProtKBP10619
[2]
Commentscatalysis
Medline ID91317848
PubMed ID1907282
JournalJ Biol Chem
Year1991
Volume266
Pages14754-62
AuthorsGaljart NJ, Morreau H, Willemsen R, Gillemans N, Bonten EJ, d'Azzo A
TitleHuman lysosomal protective protein has cathepsin A-like activity distinct from its protective function
Related UniProtKBP10619
[3]
CommentsX-ray crystallography (2.2 Angstroms)
Medline ID96164441
PubMed ID8591035
JournalStructure
Year1995
Volume3
Pages1249-59
AuthorsRudenko G, Bonten E, d'Azzo A, Hol WG
TitleThree-dimensional structure of the human 'protective protein': structure of the precursor form suggests a complex activation mechanism.
Related PDB1ivy
[4]
Commentscatalysis
PubMed ID9435242
JournalProc Natl Acad Sci U S A
Year1998
Volume95
Pages621-5
AuthorsRudenko G, Bonten E, Hol WG, d'Azzo A
TitleThe atomic model of the human protective protein/cathepsin A suggests a structural basis for galactosialidosis.
[5]
PubMed ID9878520
JournalBiochem Biophys Res Commun
Year1998
Volume253
Pages228-34
AuthorsItoh K, Naganawa Y, Kamei S, Shimmoto M, Sakuraba H
TitleStabilizing effect of lysosomal beta-galactosidase on the catalytic activity of protective protein/cathepsin A secreted by human platelets.
[6]
Commentscatalysis (mutation analysis)
PubMed ID10944848
JournalJ Hum Genet
Year2000
Volume45
Pages200-6
AuthorsTakiguchi K, Itoh K, Shimmoto M, Ozand PT, Doi H, Sakuraba H
TitleStructural and functional study of K453E mutant protective protein/cathepsin A causing the late infantile form of galactosialidosis.

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.

createdupdated
2003-01-272011-02-16


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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)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
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