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Literature summary for 3.4.22.62 extracted from

  • Huber, K.L.; Ghosh, S.; Hardy, J.A.
    Inhibition of caspase-9 by stabilized peptides targeting the dimerization interface (2012), Biopolymers, 98, 451-465.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.4.22.62

Activating Compound

Activating Compound Comment Organism Structure
additional information the zymogen caspase-9 has very low activity as a monomer. Activity increases upon dimerization and increases even more profoundly upon interaction with the apoptosome, a heptameric complex formed from association of Apaf-1 and cytochrome c in an ATP-dependent process. Caspase-9 does not require intersubunit cleavage for activation Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of His6-tagged holoenzyme in Escherichia coli strain BL21(DE3), recombinantindividual expression of large and small subunits in inclusion bodies Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
additional information development, design and synthesis, of three types of stabilized peptides derived from the alpha5 helix of inhibitor XIAP-BIR3, using incorporation of amino-isobutyric acid, the avian pancreatic polypeptide-scaffold or aliphatic staples, overview. The stabilized peptides are helical in solution and achieve good inhibition, indicating that this allosteric site at the caspase-9 dimerization interface is regulatable with low-molecular weight synthetic ligands and is thus a druggable site. Other caspases, which are not regulated by dimerization, are not inactivated by these peptides Homo sapiens
N-Fmoc-S-2-(2'-octyl)alanine
-
 Homo sapiens
N-Fmoc-S-2-(2'-pentyl)alanine
-
 Homo sapiens
XIAP-BIR3 a natural caspase-9 inhibitor that binds at the dimer interface keeping the enzyme in an inactive monomeric state, binding to the enzyme involves the alpha5 helix of XIAP-BIR3 Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
inactive procaspase-7 variant C186A + H2O Homo sapiens
-
 active caspase-7 variant C186A + ?
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
proteolytic modification when bound to the apoptosome, caspase-9 is processed at Asp315, resulting in a CARD-large subunit portion of the enzyme and a small subunit beginning with the N-terminal sequence of ATPF. Proteolytic removal of the CARD domain from the large subunit, which results in decreased activity, is also observed. Processed caspase-9 can be displaced from the apoptosome by additional molecules of procaspase-9, resulting in release of cleaved caspase-9, which can form active dimers Homo sapiens

Purification (Commentary)

Purification (Comment) Organism
recombinant His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity and anion exchange chromatography Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
inactive procaspase-7 variant C186A + H2O
-
 Homo sapiens active caspase-7 variant C186A + ?
-
 ?
additional information as a cleaved dimer, the L2 loop from one half of the dimer is able to interact with the L2' loop from the other half in the presence of substrate, similarly to other caspases. In this state, the protein is catalytically competent to process substrate. Like other caspases, caspase-9 recognizes its substrates and cleaves after specific aspartic acid residues Homo sapiens ?
-
 ?
N-acetyl-Leu-Glu-His-Asp-7-amido-4-fluorocoumarin + H2O
-
 Homo sapiens N-acetyl-Leu-Glu-His-Asp + 7-amino-4-fluorocoumarin
-
 ?

Subunits

Subunits Comment Organism
dimer processed caspase-9 can be displaced from the apoptosome by additional molecules of procaspase-9, resulting in release of cleaved caspase-9, which can form active dimers Homo sapiens
More the zymogen caspase-9 has very low activity as a monomer. Activity increases upon dimerization and increases even more profoundly upon interaction with the apoptosome. Caspase-9 does not require intersubunit cleavage for activation Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
6.5
-
 assay at Homo sapiens

General Information

General Information Comment Organism
physiological function caspase-9 is an upstream or initiator caspase that is regulated differently from all other caspases, as interaction with natural inhibitor XIAP-BIR3 occurs at the dimer interface maintaining caspase-9 in an inactive monomeric state Homo sapiens