EzCatDB: D00484
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DB codeD00484
RLCP classification1.13.200.966 : Hydrolysis
CATH domainDomain 12.40.70.10 : Cathepsin D, subunit A; domain 1Catalytic domain
Domain 22.40.70.10 : Cathepsin D, subunit A; domain 1
E.C.3.4.23.5
CSA1lya

CATH domainRelated DB codes (homologues)
2.40.70.10 : Cathepsin D, subunit A; domain 1D00471,D00436,D00438,D00439,D00440,D00441,D00442,D00443,D00437,D00444,D00423,D00445,M00206,M00166,D00231,D00529

Enzyme Name
UniProtKBKEGG

P07339
Protein nameCathepsin Dcathepsin D
SynonymsEC 3.4.23.5
ContainsCathepsin D light chain
Cathepsin D heavy chain
RefSeqNP_001900.1 (Protein)
NM_001909.4 (DNA/RNA sequence)
MEROPSA01.009 (Aspartic)
PfamPF07966 (A1_Propeptide)
PF00026 (Asp)
[Graphical view]


UniProtKB:Accession NumberP07339
Entry nameCATD_HUMAN
ActivitySpecificity similar to, but narrower than, that of pepsin A. Does not cleave the 4-Gln-|-His-5 bond in B chain of insulin.
SubunitConsists of a light chain and a heavy chain.
Subcellular locationLysosome. Melanosome. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV.
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC00017C00012C00001C00017C00012I00136
CompoundProteinPeptideH2OProteinPeptideAmino-diol-tetrahedral intermediate
Typepeptide/proteinpeptide/proteinH2Opeptide/proteinpeptide/protein
ChEBI

15377



PubChem

962
22247451



              
1lyaAUnboundUnbound UnboundUnboundUnbound
1lyaCUnboundUnbound UnboundUnboundUnbound
1lybAUnboundUnbound UnboundUnboundTransition-state-analogue:IVA-VAL-VAL-STA-ALA-STA(chain I)
1lybCUnboundUnbound UnboundUnboundTransition-state-analogue:IVA-VAL-VAL-STA-ALA-STA(chain J)
1lywAUnboundUnbound UnboundUnboundUnbound
1lywCUnboundUnbound UnboundUnboundUnbound
1lywEUnboundUnbound UnboundUnboundUnbound
1lywGUnboundUnbound UnboundUnboundUnbound
1lyaBUnboundUnbound UnboundUnboundUnbound
1lyaDUnboundUnbound UnboundUnboundUnbound
1lybBUnboundUnbound UnboundUnboundUnbound
1lybDUnboundUnbound UnboundUnboundUnbound
1lywBUnboundUnbound UnboundUnboundUnbound
1lywDUnboundUnbound UnboundUnboundUnbound
1lywFUnboundUnbound UnboundUnboundUnbound
1lywHUnboundUnbound UnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P07339
pdbCatalytic residues
         
1lyaAASP  33
1lyaCASP  33
1lybAASP  33
1lybCASP  33
1lywAASP  33
1lywCASP  33
1lywEASP  33
1lywGASP  33
1lyaBASP 231
1lyaDASP 231
1lybBASP 231
1lybDASP 231
1lywBASP 231
1lywDASP 231
1lywFASP 231
1lywHASP 231

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[8]

[9]


references
[1]
PubMed ID3202970
JournalBiol Chem Hoppe Seyler
Year1988
Volume369 Suppl
Pages323-7
AuthorsBonelli G, Kay J, Tessitore L, Jupp RA, Isidoro C, Norey CG, Autelli R, Richards AD, Baccino FM
TitlePurification and properties of cathepsin D from rat Yoshida ascites hepatoma AH-130.
[2]
PubMed ID2512908
JournalBiochem J
Year1989
Volume263
Pages601-4
AuthorsConner GE
TitleIsolation of procathepsin D from mature cathepsin D by pepstatin affinity chromatography. Autocatalytic proteolysis of the zymogen form of the enzyme.
[3]
PubMed ID2002505
JournalJ Mol Biol
Year1991
Volume218
Pages21-2
AuthorsBaudys M, Ghosh M, Harlos K, Mares M, Fusek M, Kostka V, Blake CC
TitleCrystallization and preliminary crystallographic study of cathepsin D inhibitor from potatoes.
[4]
PubMed ID1331083
JournalJ Biol Chem
Year1992
Volume267
Pages23357-63
AuthorsCantor AB, Kornfeld S
TitlePhosphorylation of Asn-linked oligosaccharides located at novel sites on the lysosomal enzyme cathepsin D.
[5]
PubMed ID1433300
JournalJ Mol Biol
Year1992
Volume227
Pages1265-8
AuthorsBieber F, Brachvogel V, Arni R, Fusek M, Metcalf P
TitleCrystallization and initial crystallographic results for pepstatin A inhibited bovine cathepsin D.
[6]
PubMed ID1640466
JournalJ Mol Biol
Year1992
Volume226
Pages555-7
AuthorsFusek M, Baudys M, Metcalf P
TitlePurification and crystallization of human cathepsin D.
[7]
PubMed ID1522590
JournalJ Mol Biol
Year1992
Volume227
Pages265-70
AuthorsGulnik S, Baldwin ET, Tarasova N, Erickson J
TitleHuman liver cathepsin D. Purification, crystallization and preliminary X-ray diffraction analysis of a lysosomal enzyme.
[8]
CommentsX-RAY CRYSTALLOGRAPHY (3 ANGSTROMS)
Medline ID93223670
PubMed ID8467789
JournalEMBO J
Year1993
Volume12
Pages1293-302
AuthorsMetcalf P, Fusek M
TitleTwo crystal structures for cathepsin D: the lysosomal targeting signal and active site.
Related UniProtKBP07339
[9]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS)
Medline ID93342076
PubMed ID8393577
JournalProc Natl Acad Sci U S A
Year1993
Volume90
Pages6796-800
AuthorsBaldwin ET, Bhat TN, Gulnik S, Hosur MV, Sowder RC 2nd, Cachau RE, Collins J, Silva AM, Erickson JW
TitleCrystal structures of native and inhibited forms of human cathepsin D: implications for lysosomal targeting and drug design.
Related PDB1lya,1lyb
Related UniProtKBP07339
[10]
PubMed ID8540315
JournalAdv Exp Med Biol
Year1995
Volume362
Pages155-66
AuthorsAguilar CF, Dhanaraj V, Guruprasad K, Dealwis C, Badasso M, Cooper JB, Wood SP, Blundell TL
TitleComparisons of the three-dimensional structures, specificities and glycosylation of renins, yeast proteinase A and cathepsin D.
[11]
PubMed ID8540317
JournalAdv Exp Med Biol
Year1995
Volume362
Pages181-92
AuthorsErickson JW, Baldwin ET, Bhat TN, Gulnik S
TitleStructure of human cathepsin D: comparison of inhibitor binding and subdomain displacement with other aspartic proteases.
[12]
PubMed ID8540327
JournalAdv Exp Med Biol
Year1995
Volume362
Pages273-8
AuthorsKoelsch G, Metcalf P, Vetvicka V, Fusek M
TitleHuman procathepsin D: three-dimensional model and isolation.
[13]
PubMed ID8540319
JournalAdv Exp Med Biol
Year1995
Volume362
Pages193-200
AuthorsMetcalf P, Fusek M
TitleCathepsin D crystal structures and lysosomal sorting.
[14]
PubMed ID7657721
JournalJ Cell Sci
Year1995
Volume108
Pages2007-15
AuthorsSchorey JS, Fortenberry SC, Chirgwin JM
TitleLysine residues in the C-terminal lobe and lysosomal targeting of procathepsin D.
[15]
PubMed ID8663051
JournalJ Biol Chem
Year1996
Volume271
Pages15590-6
AuthorsBeyer BM, Dunn BM
TitleSelf-activation of recombinant human lysosomal procathepsin D at a newly engineered cleavage junction, "short" pseudocathepsin D.
[16]
PubMed ID9195867
JournalChem Biol
Year1997
Volume4
Pages297-307
AuthorsKick EK, Roe DC, Skillman AG, Liu G, Ewing TJ, Sun Y, Kuntz ID, Ellman JA
TitleStructure-based design and combinatorial chemistry yield low nanomolar inhibitors of cathepsin D.
[17]
PubMed ID9232647
JournalProtein Sci
Year1997
Volume6
Pages1458-66
AuthorsMajer P, Collins JR, Gulnik SV, Erickson JW
TitleStructure-based subsite specificity mapping of human cathepsin D using statine-based inhibitors.
[18]
PubMed ID9561243
JournalAdv Exp Med Biol
Year1998
Volume436
Pages363-73
AuthorsSilva AM, Lee AY, Erickson JW, Goldberg DE
TitleStructural analysis of plasmepsin II. A comparison with human aspartic proteases.
[19]
PubMed ID9694859
JournalJ Biol Chem
Year1998
Volume273
Pages21067-76
AuthorsCuozzo JW, Tao K, Cygler M, Mort JS, Sahagian GG
TitleLysine-based structure responsible for selective mannose phosphorylation of cathepsin D and cathepsin L defines a common structural motif for lysosomal enzyme targeting.
[20]
CommentsX-ray crystallography
PubMed ID9783744
JournalNat Struct Biol
Year1998
Volume5
Pages866-71
AuthorsLee AY, Gulnik SV, Erickson JW
TitleConformational switching in an aspartic proteinase.
Related PDB1lyw
[21]
PubMed ID9514263
JournalProtein Sci
Year1998
Volume7
Pages88-95
AuthorsBeyer BM, Dunn BM
TitlePrime region subsite specificity characterization of human cathepsin D: the dominant role of position 128.
[22]
PubMed ID9890884
JournalBiochemistry
Year1999
Volume38
Pages73-80
AuthorsLukong KE, Elsliger MA, Mort JS, Potier M, Pshezhetsky AV
TitleIdentification of UDP-N-acetylglucosamine-phosphotransferase-binding sites on the lysosomal proteases, cathepsins A, B, and D.
[23]
PubMed ID11731271
JournalMatrix Biol
Year2001
Volume20
Pages543-53
AuthorsHandley CJ, Mok MT, Ilic MZ, Adcocks C, Buttle DJ, Robinson HC
TitleCathepsin D cleaves aggrecan at unique sites within the interglobular domain and chondroitin sulfate attachment regions that are also cleaved when cartilage is maintained at acid pH.
[24]
PubMed ID11687971
JournalOncogene
Year2001
Volume20
Pages6920-9
AuthorsGlondu M, Coopman P, Laurent-Matha V, Garcia M, Rochefort H, Liaudet-Coopman E
TitleA mutated cathepsin-D devoid of its catalytic activity stimulates the growth of cancer cells.
[25]
PubMed ID11906282
JournalJ Med Chem
Year2002
Volume45
Pages1412-9
AuthorsHuo S, Wang J, Cieplak P, Kollman PA, Kuntz ID
TitleMolecular dynamics and free energy analyses of cathepsin D-inhibitor interactions: insight into structure-based ligand design.
[26]
PubMed ID12350228
JournalBiochem J
Year2003
Volume369
Pages55-62
AuthorsPartanen S, Storch S, Loffler HG, Hasilik A, Tyynela J, Braulke T
TitleA replacement of the active-site aspartic acid residue 293 in mouse cathepsin D affects its intracellular stability, processing and transport in HEK-293 cells.
[27]
PubMed ID14695825
JournalJ Med Chem
Year2004
Volume47
Pages110-22
AuthorsErsmark K, Feierberg I, Bjelic S, Hamelink E, Hackett F, Blackman MJ, Hulten J, Samuelsson B, Aqvist J, Hallberg A
TitlePotent inhibitors of the Plasmodium falciparum enzymes plasmepsin I and II devoid of cathepsin D inhibitory activity.

comments
This enzyme belongs to the peptidase family-A1. This enzyme is composed of two chains, light chain and heavy chain.
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)

createdupdated
2004-03-032012-06-28


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
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)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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