EzCatDB: D00522
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DB codeD00522
RLCP classification1.13.30100.40 : Hydrolysis
CATH domainDomain 13.40.50.1460 : Rossmann foldCatalytic domain
Domain 23.-.-.-
E.C.3.4.22.36

CATH domainRelated DB codes (homologues)
3.40.50.1460 : Rossmann foldT00257

Enzyme Name
UniProtKBKEGG

P29466
Protein nameCaspase-1caspase-1
interleukin 1beta-converting enzyme
protease VII
protease A
interleukin 1beta precursor proteinase
interleukin 1 converting enzyme
interleukin 1beta-converting endopeptidase
interleukin-1beta convertase
interleukin-1beta converting enzyme
interleukin-1beta precursor proteinase
prointerleukin 1beta protease
precursor interleukin-1beta converting enzyme
pro-interleukin 1beta proteinase
ICE
SynonymsCASP-1
EC 3.4.22.36
Interleukin-1 beta convertase
IL-1BC
Interleukin-1 beta-converting enzyme
IL-1 beta-converting enzyme
ICE
p45
ContainsCaspase-1 subunit p20
Caspase-1 subunit p10
RefSeqNP_001214.1 (Protein)
NM_001223.4 (DNA/RNA sequence)
NP_001244047.1 (Protein)
NM_001257118.1 (DNA/RNA sequence)
NP_001244048.1 (Protein)
NM_001257119.1 (DNA/RNA sequence)
NP_150634.1 (Protein)
NM_033292.3 (DNA/RNA sequence)
NP_150635.1 (Protein)
NM_033293.3 (DNA/RNA sequence)
NP_150636.1 (Protein)
NM_033294.3 (DNA/RNA sequence)
NP_150637.1 (Protein)
NM_033295.3 (DNA/RNA sequence)
MEROPSC14.001 (Cysteine)
PfamPF00619 (CARD)
PF00656 (Peptidase_C14)
[Graphical view]


UniProtKB:Accession NumberP29466
Entry nameCASP1_HUMAN
ActivityStrict requirement for an Asp residue at position P1 and has a preferred cleavage sequence of Tyr-Val-Ala- Asp-|-.
SubunitHeterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (p20) and a 10 kDa (p10) subunit. The p20 subunit can also form a heterodimer with the epsilon isoform which then has an inhibitory effect. May be a component of the inflammasome, a protein complex which also includes PYCARD, CARD8 and NALP2 and whose function would be the activation of proinflammatory caspases. Interacts with INCA.
Subcellular locationCytoplasm.
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idL00099L00101C00001L00100L00102C00218I00153I00154I00155
Compoundinterleukin 1-beta precursorACE-TYR-VAL-ALA-ASP-|-NHMecH2Ointerleukin 1-betaACE-TYR-VAL-ALA-ASPMethylaminePeptidyl-Cys-tetrahedral-intermediate (with previous peptide)Acyl-enzyme(Peptidyl-Cys-acyl group)Peptidyl-Cys-tetrahedral-intermediate
Typepeptide/proteinamine group,aromatic ring (only carbon atom),carbohydrate,carboxyl group,peptide/proteinH2Opeptide/proteinaromatic ring (only carbon atom),carbohydrate,carboxyl group,peptide/proteinamine group


ChEBI

15377


16830



PubChem

962
22247451

15931057
6329



                 
1bmqAUnboundUnbound UnboundUnboundUnboundUnboundIntermediate-analogue:MNOUnbound
1ibcAUnboundUnbound UnboundUnboundUnboundUnboundIntermediate-analogue:ACE-TRP-GLU-HIS-ASA(chain C)Unbound
1iceAUnboundUnbound UnboundUnboundUnboundUnboundIntermediate-analogue:ACE-TYR-VAL-ALA-ASA(chain T)Unbound
1bmqBUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnbound
1ibcBUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnbound
1iceBUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot, literature
pdbCatalytic residues
         
1bmqAHIS 237;CYS 285
1ibcAHIS 237;CYS 285
1iceAHIS 237;CYS 285
1bmqB 
1ibcB 
1iceB 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]p.270-271, p.273-274, Fig.53
[2]p.349, Fig.4
[3]p.4, p.7-8
[5]p.7226-7227, Fig.2
[7]Fig.5

references
[1]
CommentsX-ray crystallography
PubMed ID8035875
JournalNature
Year1994
Volume370
Pages270-5
AuthorsWilson KP, Black JA, Thomson JA, Kim EE, Griffith JP, Navia MA, Murcko MA, Chambers SP, Aldape RA, Raybuck SA, et al
TitleStructure and mechanism of interleukin-1 beta converting enzyme.
Related PDB1ice
[2]
PubMed ID8044845
JournalCell
Year1994
Volume78
Pages343-52
AuthorsWalker NP, Talanian RV, Brady KD, Dang LC, Bump NJ, Ferenz CR, Franklin S, Ghayur T, Hackett MC, Hammill LD, et al
TitleCrystal structure of the cysteine protease interleukin-1 beta-converting enzyme: a (p20/p10)2 homodimer.
[3]
PubMed ID7773174
JournalProtein Sci
Year1995
Volume4
Pages3-12
AuthorsThornberry NA, Molineaux SM
TitleInterleukin-1 beta converting enzyme: a novel cysteine protease required for IL-1 beta production and implicated in programmed cell death.
[4]
PubMed ID8535252
JournalProtein Sci
Year1995
Volume4
Pages2149-55
AuthorsMalinowski JJ, Grasberger BL, Trakshel G, Huston EE, Helaszek CT, Smallwood AM, Ator MA, Banks TM, Brake PG, Ciccarelli RB, et al
TitleProduction, purification, and crystallization of human interleukin-1 beta converting enzyme derived from an Escherichia coli expression system.
[5]
PubMed ID9054418
JournalJ Biol Chem
Year1997
Volume272
Pages7223-8
AuthorsMargolin N, Raybuck SA, Wilson KP, Chen W, Fox T, Gu Y, Livingston DJ
TitleSubstrate and inhibitor specificity of interleukin-1 beta-converting enzyme and related caspases.
[6]
CommentsX-ray crystallography
PubMed ID9190289
JournalChem Biol
Year1997
Volume4
Pages149-55
AuthorsRano TA, Timkey T, Peterson EP, Rotonda J, Nicholson DW, Becker JW, Chapman KT, Thornberry NA
TitleA combinatorial approach for determining protease specificities: application to interleukin-1beta converting enzyme (ICE).
Related PDB1ibc
[7]
PubMed ID9987822
JournalChem Pharm Bull (Tokyo)
Year1999
Volume47
Pages11-21
AuthorsOkamoto Y, Anan H, Nakai E, Morihira K, Yonetoku Y, Kurihara H, Sakashita H, Terai Y, Takeuchi M, Shibanuma T, Isomura Y
TitlePeptide based interleukin-1 beta converting enzyme (ICE) inhibitors: synthesis, structure activity relationships and crystallographic study of the ICE-inhibitor complex.
Related PDB1bmq

comments
This enzyme belongs to the peptidase family-C14.
This enzyme is one of cysteine protease. According to the literature [1], Cys285 acts as a nucleophile, which would be activated by His237, to form a tetrahedral intermediate. This tetrahedral intermedate results in acyl-intermediate, by His237 protonating amino group of the leaving ligand. The acyl-intermediate is attacked by a water molecule, which is activated by His237, to form a tetrahedral intermediate again, finally leaving the peptide product.
During the catalytis, the tetrahedral intermedate is stabilized by the backbone amide protons of Cys285 and Gly238 (see [1]).

createdupdated
2002-07-042012-10-22


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