DB code: D00522

RLCP classification	1.13.30100.40 : Hydrolysis
CATH domain	3.40.50.1460 : Rossmann fold	Catalytic domain
CATH 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

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 15377			16830 16830
PubChem			22247451 962 22247451 962		15931057 15931057	6329 6329

1bmqA	Unbound	Unbound		Unbound	Unbound	Unbound	Unbound	Intermediate-analogue:MNO	Unbound
1ibcA	Unbound	Unbound		Unbound	Unbound	Unbound	Unbound	Intermediate-analogue:ACE-TRP-GLU-HIS-ASA (chain C)	Unbound
1iceA	Unbound	Unbound		Unbound	Unbound	Unbound	Unbound	Intermediate-analogue:ACE-TYR-VAL-ALA-ASA (chain T)	Unbound
1bmqB	Unbound	Unbound		Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1ibcB	Unbound	Unbound		Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1iceB	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	HIS 237;CYS 285
1ibcA	HIS 237;CYS 285
1iceA	HIS 237;CYS 285
1bmqB
1ibcB
1iceB

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]).

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