EzCatDB: D00443

DB codeD00443
RLCP classification1.13.200.966
CATH domainDomain 12.40.70.10Catalytic domain
Domain 22.40.70.10Catalytic domain
E.C.3.4.23.24
CSA1eag

CATH domainRelated DB codes (homologues)
2.40.70.10D00471,D00436,D00438,D00439,D00440,D00441,D00442,D00437,D00444,D00423,D00445,D00484,M00206,M00166,D00231,D00529

Enzyme Name
Swiss-protKEGG

P0CS83Q00663
Protein name
Candidapepsincandidapepsin
Candida albicans aspartic proteinase
Candida albicans carboxyl proteinase
Candida albicans secretory acid proteinase
Candida olea acid proteinase
Candida aspartic proteinase
Candida olea aspartic proteinase
Candida albicans aspartic proteinase
SynonymsNoneEC 3.4.23.24
Aspartate protease
ACP


Swiss-prot:Accession NumberP0CS83Q00663
Entry nameCARP2_CANAXCARP_CANTR
ActivityPreferential cleavage at the carboxyl of hydrophobic amino acids, but fails to cleave 15-Leu-|-Tyr-16, 16-Tyr-|-Leu-17 and 24-Phe-|-Phe-25 of insulin B chain. Activates trypsinogen, and degrades keratin.Preferential cleavage at the carboxyl of hydrophobic amino acids, but fails to cleave 15-Leu-|-Tyr-16, 16-Tyr-|-Leu-17 and 24-Phe-|-Phe-25 of insulin B chain. Activates trypsinogen, and degrades keratin.
SubunitMonomer.
Subcellular locationSecreted.Secreted.
Cofactor



SubstratesProductsintermediates
KEGG-idC00017C00012L00076L00077C00001C00017C00012C00298I00136
CompoundProteinPeptideTrypsinogenKeratinH2OProteinPeptideTrypsinAmino-diol-tetrahedral intermediate
Typepeptide/proteinpeptide/proteinpeptide/proteinpeptide/proteinH2Opeptide/proteinpeptide/proteinpeptide/protein
1eagA01UnboundUnboundUnboundUnbound
UnboundUnboundUnboundTransition-state-analogue:A70
1zapA01UnboundUnboundUnboundUnbound
UnboundUnboundUnboundTransition-state-analogue:A70
3pvkA01UnboundUnboundUnboundUnbound
UnboundAnalogue:BAM 3001UnboundUnbound
3q70A01UnboundUnboundUnboundUnbound
UnboundUnboundUnboundTransition-state-analogue:RIT
1j71A01UnboundUnboundUnboundUnbound
UnboundBound:THR-ILE-THR-SER(chain B)UnboundUnbound
1eagA02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1zapA02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound
3pvkA02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound
3q70A02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1j71A02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P28871, Q00663
pdbCatalytic residues
1eagA01ASP 32
1zapA01ASP 32
3pvkA01ASP 32
3q70A01ASP 32
1j71A01ASP 32
1eagA02ASP 218
1zapA02ASP 218
3pvkA02ASP 218
3q70A02ASP 218
1j71A02ASP 218

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]Fig.5, p.7010-70123
[6]

[9]p.12706-12708

references
[1]
PubMed ID3313384
JournalProc Natl Acad Sci U S A
Year1987
Volume84
Pages7009-13
AuthorsSuguna K, Padlan EA, Smith CW, Carlson WD, Davies DR
TitleBinding of a reduced peptide inhibitor to the aspartic proteinase from Rhizopus chinensis: implications for a mechanism of action.
[2]
PubMed ID8263928
JournalJ Mol Biol
Year1993
Volume234
Pages1266-9
AuthorsCutfield S, Marshall C, Moody P, Sullivan P, Cutfield J
TitleCrystallization of inhibited aspartic proteinase from Candida albicans.
[3]
PubMed ID8162186
JournalMicrobiology
Year1994
Volume140
Pages167-71
AuthorsTsushima H, Mine H, Kawakami Y, Hyodoh F, Ueki A
TitleCandida albicans aspartic proteinase cleaves and inactivates human epidermal cysteine proteinase inhibitor, cystatin A.
[4]
PubMed ID8540363
JournalAdv Exp Med Biol
Year1995
Volume362
Pages489-500
AuthorsFusek M, Smith E, Foundling SI
TitleExtracellular aspartic proteinases from Candida yeasts.
[5]
PubMed ID7599606
JournalFEMS Immunol Med Microbiol
Year1995
Volume11
Pages69-72
AuthorsTsushima H, Mine H
TitleCleavage of human big endothelin-1 by Candida albicans aspartic proteinase.
[6]
CommentsX-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
Medline ID96164442
PubMed ID8591036
JournalStructure
Year1995
Volume3
Pages1261-71
AuthorsCutfield SM, Dodson EJ, Anderson BF, Moody PC, Marshall CJ, Sullivan PA, Cutfield JF
TitleThe crystal structure of a major secreted aspartic proteinase from Candida albicans in complexes with two inhibitors.
Related PDB1eag
Related Swiss-protP28871
[7]
CommentsX-ray crystallography
PubMed ID8845753
JournalProtein Sci
Year1996
Volume5
Pages640-52
AuthorsAbad-Zapatero C, Goldman R, Muchmore SW, Hutchins C, Stewart K, Navaza J, Payne CD, Ray TL
TitleStructure of a secreted aspartic protease from C. albicans complexed with a potent inhibitor: implications for the design of antifungal agents.
Related PDB1zap
[8]
CommentsCHARACTERIZATION.
Medline ID97195781
PubMed ID9043112
JournalMicrobiology
Year1997
Volume143
Pages349-56
AuthorsSmolenski G, Sullivan PA, Cutfield SM, Cutfield JF
TitleAnalysis of secreted aspartic proteinases from Candida albicans: purification and characterization of individual Sap1, Sap2 and Sap3 isoenzymes.
Related Swiss-protP28871
[9]
PubMed ID9335526
JournalBiochemistry
Year1997
Volume36
Pages12700-10
AuthorsSymersky J, Monod M, Foundling SI
TitleHigh-resolution structure of the extracellular aspartic proteinase from Candida tropicalis yeast.
[10]
PubMed ID9741846
JournalProteins
Year1998
Volume33
Pages74-87
AuthorsSchnecke V, Swanson CA, Getzoff ED, Tainer JA, Kuhn LA
TitleScreening a peptidyl database for potential ligands to proteins with side-chain flexibility.
[11]
PubMed ID11375761
JournalCurr Med Chem
Year2001
Volume8
Pages941-8
AuthorsStewart K, Abad-Zapatero C
TitleCandida proteases and their inhibition: prospects for antifungal therapy.
[12]
PubMed ID11678651
JournalJ Nat Prod
Year2001
Volume64
Pages1282-5
AuthorsLi XC, Jacob MR, Pasco DS, ElSohly HN, Nimrod AC, Walker LA, Clark AM
TitlePhenolic compounds from Miconia myriantha inhibiting Candida aspartic proteases.
[13]
PubMed ID12141856
JournalJ Nat Prod
Year2002
Volume65
Pages979-85
AuthorsZhang Z, ElSohly HN, Jacob MR, Pasco DS, Walker LA, Clark AM
TitleNatural products inhibiting Candida albicans secreted aspartic proteases from Lycopodium cernuum.
[14]
PubMed ID12088427
JournalJ Nat Prod
Year2002
Volume65
Pages856-9
AuthorsZhang Z, ElSohly HN, Jacob MR, Pasco DS, Walker LA, Clark AM
TitleNew sesquiterpenoids from the root of Guatteria multivenia.
[15]
PubMed ID12637026
JournalBiochim Biophys Acta
Year2003
Volume1646
Pages184-95
AuthorsBackman D, Danielson UH
TitleKinetic and mechanistic analysis of the association and dissociation of inhibitors interacting with secreted aspartic acid proteases 1 and 2 from Candida albicans.
[16]
PubMed ID22213702
JournalChemMedChem
Year2012
Volume7
Pages248-61
AuthorsBehnen J, Koster H, Neudert G, Craan T, Heine A, Klebe G
TitleExperimental and computational active site mapping as a starting point to fragment-based lead discovery.
Related PDB3pvk

comments
This enzyme belongs to the peptidase family-A1.
According to the literature [6] & [7], this enzyme has got a catalytic dyad composed of two aspartate residues, supporting the catalytic mechanism proposed by the paper [1].
Accoriding to the proposed mechanism (see [1]), the sidechains of both the aspartic acid residues are hydrogen-bonded to the catalytic water.
The sidechain of the ionized aspartate (possibly corresponding to Asp218 of 1eag) might act as a general base, which can abstract a proton from the water, which in turn would make a nucleophilic attack on the carbonyl carbon of the peptide bond.
Meanwhile, the protonated sidechain of the other aspartate (corresponding to Asp32 of 1eag) may stabilize the negative charge on the carbonyl oxygen of the scissile bond during the transition state.
At the next stage, the sidechain of the aspartate that had accepted a proton from water could protonate the leaving nitrogen atom, as a general acid, during the cleavage of the peptide bond.

createdupdated
2004-04-302012-06-26
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 2010)
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)

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