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Literature summary for 3.4.22.56 extracted from

  • Fang, B.; Fu, G.; Agniswamy, J.; Harrison, R.W.; Weber, I.T.
    Caspase-3 binds diverse P4 residues in peptides as revealed by crystallography and structural modeling (2009), Apoptosis, 14, 741-752.
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
expression in Escherichia coli strain BL21(DE3) Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
recombinant enzyme in complex with inhibitors Ac-IEPD-Cho, Ac-WEHD-Cho, Ac-YVADCho, and Boc-D(OMe)-fluoromethyl ketone, caspase-3 is incubated at room temperature with the inhibitor at 10 to 20fold molar excess, followed by crystallization via the hanging-drop vapor diffusion method, 0.001 ml of 4 mg/ml protein in solution is mixed with an equal volume of mother liquid containing 100 mM sodium citrate, 5% glycerol, 10 mM DTT, and 14-18% PEG 6000, pH 6.5, 24 h at room temperature, X-ray diffraction structure determination and analysis at 1.9-2.6 A resolution, molecular replacement, modelling, overview Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
Ac-DEVD-CHO
-
Homo sapiens
Ac-DMQD-CHO
-
Homo sapiens
Ac-DQMD-CHO
-
Homo sapiens
Ac-IEPD-CHO a reversible aldehyde caspase-3 inhibitor, bound in extended conformation in the S1-S4 substrate binding sites of caspase-3, binding structure with hydrogen bond and ionic interactions, overview Homo sapiens
Ac-WEHD-CHO a reversible aldehyde caspase-3 inhibitor, bound in extended conformation in the S1-S4 substrate binding sites of caspase-3, binding structure with hydrogen bond and ionic interactions, overview Homo sapiens
Ac-YVAD-CHO a reversible aldehyde caspase-3 inhibitor, bound in extended conformation in the S1-S4 substrate binding sites of caspase-3, binding structure with hydrogen bond and ionic interactions, overview Homo sapiens
Boc-D(OMe)-fluoromethyl ketone a pan-caspase irreversible inhibitor Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0625
-
DEVD-4-nitroanilide
-
Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens caspases are key effectors in the processes of apoptosis and inflammation, executioner caspases selectively hydrolyze cellular proteins in the pathways leading to cell death ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P42574
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant enzyme from Escherichia coli by nickel affinity chromatography, ion exchange chromatography, and gel filtration Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
DEVD-4-nitroanilide + H2O
-
Homo sapiens DEVD + 4-nitroaniline
-
?
additional information caspases are key effectors in the processes of apoptosis and inflammation, executioner caspases selectively hydrolyze cellular proteins in the pathways leading to cell death Homo sapiens ?
-
?
additional information caspase-3 recognizes various P4 residues in its numerous protein substrates, Asp is the most frequent P4 residue in peptide substrates. Although a wide variety of P4 residues in the cellular proteins are cleaved by caspase-3. Hydrophobic residues appear in the relative frequency of Val-Ala-Leu-Met-Phe-Ile/Cys in descending order. The P4 residues forms favorable hydrophobic interactions in two separate hydrophobic regions of the binding site. The side chains of P4 Ile and Tyr form hydrophobic interactions with caspase-3 residues Trp206 and Trp214 within a non-polar pocket of the S4 subsite, while P4 Trp interacts with Phe250 and Phe252 that can also form the S5 subsite, adaptability of caspase-3 for binding diverse P4 residues, substrate specificity, overview Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
More caspase-3 belongs to the group of executioner caspases of the family of cysteine aspartyl proteases Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0000012
-
-
Homo sapiens Ac-DEVD-CHO
0.000012
-
-
Homo sapiens Ac-DMQD-CHO
0.0012
-
-
Homo sapiens Ac-IEPD-CHO
0.0019
-
-
Homo sapiens Ac-WEHD-CHO
0.01
-
-
Homo sapiens Ac-YVAD-CHO