DB code: D00522

RLCP classification 1.13.30100.40 : Hydrolysis
CATH domain 3.40.50.1460 : Rossmann fold Catalytic domain
3.-.-.- :
E.C. 3.4.22.36
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.50.1460 : Rossmann fold T00257

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Contains RefSeq MEROPS Pfam
P29466 Caspase-1
CASP-1
EC 3.4.22.36
Interleukin-1 beta convertase
IL-1BC
Interleukin-1 beta-converting enzyme
IL-1 beta-converting enzyme
ICE
p45
Caspase-1 subunit p20
Caspase-1 subunit p10
NP_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)
C14.001 (Cysteine)
PF00619 (CARD)
PF00656 (Peptidase_C14)
[Graphical View]

KEGG enzyme name
caspase-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

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P29466 CASP1_HUMAN Strict requirement for an Asp residue at position P1 and has a preferred cleavage sequence of Tyr-Val-Ala- Asp-|-. Heterotetramer 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. Cytoplasm.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id L00099 L00101 C00001 L00100 L00102 C00218 I00153 I00154 I00155
E.C.
Compound interleukin 1-beta precursor ACE-TYR-VAL-ALA-ASP-|-NHMec H2O interleukin 1-beta ACE-TYR-VAL-ALA-ASP Methylamine Peptidyl-Cys-tetrahedral-intermediate (with previous peptide) Acyl-enzyme(Peptidyl-Cys-acyl group) Peptidyl-Cys-tetrahedral-intermediate
Type peptide/protein amine group,aromatic ring (only carbon atom),carbohydrate,carboxyl group,peptide/protein H2O peptide/protein aromatic ring (only carbon atom),carbohydrate,carboxyl group,peptide/protein amine group
ChEBI 15377
16830
PubChem 22247451
962
15931057
6329
1bmqA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:MNO Unbound
1ibcA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:ACE-TRP-GLU-HIS-ASA (chain C) Unbound
1iceA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:ACE-TYR-VAL-ALA-ASA (chain T) Unbound
1bmqB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ibcB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1iceB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot, literature

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1bmqA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 237;CYS 285
1ibcA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 237;CYS 285
1iceA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 237;CYS 285
1bmqB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ibcB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1iceB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.270-271, p.273-274, Fig.5 3
[2]
p.349, Fig.4
[3]
p.4, p.7-8
[5]
p.7226-7227, Fig.2
[7]
Fig.5

References
[1]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 8035875
Journal Nature
Year 1994
Volume 370
Pages 270-5
Authors Wilson KP, Black JA, Thomson JA, Kim EE, Griffith JP, Navia MA, Murcko MA, Chambers SP, Aldape RA, Raybuck SA, et al
Title Structure and mechanism of interleukin-1 beta converting enzyme.
Related PDB 1ice
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 8044845
Journal Cell
Year 1994
Volume 78
Pages 343-52
Authors Walker NP, Talanian RV, Brady KD, Dang LC, Bump NJ, Ferenz CR, Franklin S, Ghayur T, Hackett MC, Hammill LD, et al
Title Crystal structure of the cysteine protease interleukin-1 beta-converting enzyme: a (p20/p10)2 homodimer.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 7773174
Journal Protein Sci
Year 1995
Volume 4
Pages 3-12
Authors Thornberry NA, Molineaux SM
Title Interleukin-1 beta converting enzyme: a novel cysteine protease required for IL-1 beta production and implicated in programmed cell death.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8535252
Journal Protein Sci
Year 1995
Volume 4
Pages 2149-55
Authors Malinowski JJ, Grasberger BL, Trakshel G, Huston EE, Helaszek CT, Smallwood AM, Ator MA, Banks TM, Brake PG, Ciccarelli RB, et al
Title Production, purification, and crystallization of human interleukin-1 beta converting enzyme derived from an Escherichia coli expression system.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 9054418
Journal J Biol Chem
Year 1997
Volume 272
Pages 7223-8
Authors Margolin N, Raybuck SA, Wilson KP, Chen W, Fox T, Gu Y, Livingston DJ
Title Substrate and inhibitor specificity of interleukin-1 beta-converting enzyme and related caspases.
Related PDB
Related UniProtKB
[6]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9190289
Journal Chem Biol
Year 1997
Volume 4
Pages 149-55
Authors Rano TA, Timkey T, Peterson EP, Rotonda J, Nicholson DW, Becker JW, Chapman KT, Thornberry NA
Title A combinatorial approach for determining protease specificities: application to interleukin-1beta converting enzyme (ICE).
Related PDB 1ibc
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 9987822
Journal Chem Pharm Bull (Tokyo)
Year 1999
Volume 47
Pages 11-21
Authors Okamoto Y, Anan H, Nakai E, Morihira K, Yonetoku Y, Kurihara H, Sakashita H, Terai Y, Takeuchi M, Shibanuma T, Isomura Y
Title Peptide based interleukin-1 beta converting enzyme (ICE) inhibitors: synthesis, structure activity relationships and crystallographic study of the ICE-inhibitor complex.
Related PDB 1bmq
Related UniProtKB

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]).

Created Updated
2002-07-04 2012-10-22