DB code: D00231

RLCP classification 1.13.200.966 : Hydrolysis
CATH domain 2.40.70.10 : Cathepsin D, subunit A; domain 1 Catalytic domain
2.40.70.10 : Cathepsin D, subunit A; domain 1 Catalytic domain
E.C. 3.4.23.25
CSA 2jxr
M-CSA 2jxr
MACiE

CATH domain Related DB codes (homologues)
2.40.70.10 : Cathepsin D, subunit A; domain 1 D00471 D00436 D00438 D00439 D00440 D00441 D00442 D00443 D00437 D00444 D00423 D00445 D00484 M00206 M00166 D00529

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq MEROPS Pfam
P07267 Saccharopepsin
EC 3.4.23.25
Aspartate protease
Proteinase A
Proteinase YSCA
Carboxypeptidase Y-deficient protein 4
NP_015171.1 (Protein)
NM_001183968.1 (DNA/RNA sequence)
A01.018 (Aspartic)
PF00026 (Asp)
[Graphical View]

KEGG enzyme name
saccharopepsin
yeast endopeptidase A
Saccharomyces aspartic proteinase
aspartic proteinase yscA
proteinase A
proteinase yscA
yeast proteinase A
Saccharomyces cerevisiae aspartic proteinase A
yeast proteinase A
PRA

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P07267 CARP_YEAST Hydrolysis of proteins with broad specificity for peptide bonds. Cleaves -Leu-Leu-|-Val-Tyr- bond in a synthetic substrate. Does not act on esters of Tyr or Arg. Vacuole. Note=Lysosome-like vacuoles.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00017 C00012 C00001 C00017 C00012 I00136
E.C.
Compound Protein Peptide H2O Protein Peptide Amino-diol-tetrahedral intermediate
Type peptide/protein peptide/protein H2O peptide/protein peptide/protein
ChEBI 15377
15377
PubChem 22247451
962
22247451
962
1dp5A01 Unbound Unbound Unbound Unbound Unbound
1dpjA01 Unbound Unbound Unbound Unbound Unbound
1fmuA01 Unbound Unbound Unbound Unbound Unbound
1fmxA01 Unbound Unbound Unbound Unbound Unbound
1fmxB01 Unbound Unbound Unbound Unbound Unbound
1fq4A01 Unbound Analogue:2Y2 Unbound Unbound Unbound
1fq5A01 Unbound Analogue:0GM Unbound Unbound Unbound
1fq6A01 Unbound Analogue:0QF Unbound Unbound Unbound
1fq7A01 Unbound Analogue:2Y3 Unbound Unbound Unbound
1fq8A01 Unbound Analogue:2Y4 Unbound Unbound Unbound
1g0vA01 Unbound Unbound Unbound Unbound Unbound
1jxrA01 Unbound Unbound Unbound Unbound Transition-state-analogue:MOR-PHE-NLE-CHF-NME (chain I)
2jxrA01 Unbound Unbound Unbound Unbound Transition-state-analogue:2Z3
1dp5A02 Unbound Unbound Unbound Unbound Unbound
1dpjA02 Unbound Unbound Unbound Unbound Unbound
1fmuA02 Unbound Unbound Unbound Unbound Unbound
1fmxA02 Unbound Unbound Unbound Unbound Unbound
1fmxB02 Unbound Unbound Unbound Unbound Unbound
1fq4A02 Unbound Unbound Unbound Unbound Unbound
1fq5A02 Unbound Unbound Unbound Unbound Unbound
1fq6A02 Unbound Unbound Unbound Unbound Unbound
1fq7A02 Unbound Unbound Unbound Unbound Unbound
1fq8A02 Unbound Unbound Unbound Unbound Unbound
1g0vA02 Unbound Unbound Unbound Unbound Unbound
1jxrA02 Unbound Unbound Unbound Unbound Unbound
2jxrA02 Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P07267

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1dp5A01 ASP 32
1dpjA01 ASP 32
1fmuA01 ASP 32
1fmxA01 ASP 33
1fmxB01 ASP 33
1fq4A01 ASP 32
1fq5A01 ASP 32
1fq6A01 ASP 32
1fq7A01 ASP 32
1fq8A01 ASP 32
1g0vA01 ASP 32
1jxrA01 ASP 32
2jxrA01 ASP 32
1dp5A02 ASP 215
1dpjA02 ASP 215
1fmuA02 ASP 217
1fmxA02 ASP 218
1fmxB02 ASP 218
1fq4A02 ASP 215
1fq5A02 ASP 215
1fq6A02 ASP 215
1fq7A02 ASP 215
1fq8A02 ASP 215
1g0vA02 ASP 215
1jxrA02 ASP 215 mutant L315I
2jxrA02 ASP 215 mutant L315I

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[3]

References
[1]
Resource
Comments
Medline ID
PubMed ID 1959673
Journal FEBS Lett
Year 1991
Volume 293
Pages 62-6
Authors Rupp S, Hirsch HH, Wolf DH
Title Biogenesis of the yeast vacuole (lysosome). Active site mutation in the vacuolar aspartate proteinase yscA blocks maturation of vacuolar proteinases.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 8540315
Journal Adv Exp Med Biol
Year 1995
Volume 362
Pages 155-66
Authors Aguilar CF, Dhanaraj V, Guruprasad K, Dealwis C, Badasso M, Cooper JB, Wood SP, Blundell TL
Title Comparisons of the three-dimensional structures, specificities and glycosylation of renins, yeast proteinase A and cathepsin D.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS)
Medline ID 97280793
PubMed ID 9135120
Journal J Mol Biol
Year 1997
Volume 267
Pages 899-915
Authors Aguilar CF, Cronin NB, Badasso M, Dreyer T, Newman MP, Cooper JB, Hoover DJ, Wood SP, Johnson MS, Blundell TL
Title The three-dimensional structure at 2.4 A resolution of glycosylated proteinase A from the lysosome-like vacuole of Saccharomyces cerevisiae.
Related PDB 1jxr 2jxr
Related UniProtKB P07267
[4]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11061973
Journal J Mol Biol
Year 2000
Volume 303
Pages 745-60
Authors Cronin NB, Badasso MO, J Tickle I, Dreyer T, Hoover DJ, Rosati RL, Humblet CC, Lunney EA, Cooper JB
Title X-ray structures of five renin inhibitors bound to saccharopepsin: exploration of active-site specificity.
Related PDB 1fq4 1fq5 1fq6 1fq7 1fq8
Related UniProtKB
[5]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10655612
Journal Nat Struct Biol
Year 2000
Volume 7
Pages 113-7
Authors Li M, Phylip LH, Lees WE, Winther JR, Dunn BM, Wlodawer A, Kay J, Gustchina A
Title The aspartic proteinase from Saccharomyces cerevisiae folds its own inhibitor into a helix.
Related PDB 1dp5 1dpj
Related UniProtKB
[6]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11042188
Journal J Biol Chem
Year 2001
Volume 276
Pages 2023-30
Authors Phylip LH, Lees WE, Brownsey BG, Bur D, Dunn BM, Winther JR, Gustchina A, Li M, Copeland T, Wlodawer A, Kay J
Title The potency and specificity of the interaction between the IA3 inhibitor and its target aspartic proteinase from Saccharomyces cerevisiae.
Related PDB 1g0v
Related UniProtKB
[7]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 12127998
Journal Biochem Biophys Res Commun
Year 2002
Volume 295
Pages 1020-6
Authors Gustchina A, Li M, Phylip LH, Lees WE, Kay J, Wlodawer A
Title An unusual orientation for Tyr75 in the active site of the aspartic proteinase from Saccharomyces cerevisiae.
Related PDB 1fmu 1fmx
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 15065849
Journal Biochemistry
Year 2004
Volume 43
Pages 4071-81
Authors Green TB, Ganesh O, Perry K, Smith L, Phylip LH, Logan TM, Hagen SJ, Dunn BM, Edison AS
Title IA3, an aspartic proteinase inhibitor from Saccharomyces cerevisiae, is intrinsically unstructured in solution.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the peptidase family-A1. As it has a catalytic dyad composed of two aspartic acid residues, it must have a similar mechanism to that of pepsin (D00436 in EzCatDB).

Created Updated
2004-03-25 2012-06-27