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Literature summary for 3.4.22.59 extracted from

  • MacPherson, D.J.; Mills, C.L.; Ondrechen, M.J.; Hardy, J.A.
    Tri-arginine exosite patch of caspase-6 recruits substrates for hydrolysis (2019), J. Biol. Chem., 294, 71-88 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.4.22.59

Cloned(Commentary)

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

Protein Variants

Protein Variants Comment Organism
R42A/R43A/R44A substitutions of the tri-arginine patch Arg-42-Arg-44 markedly alters rates of protein substrate hydrolysis. Turnover of protein substrates but not of short peptide substrates is affected. The mutant is unable to fully hydrolyze itself to the mature form Homo sapiens
R44K cancer-associated mutation markedly alters rates of protein substrate hydrolysis. Turnover of protein substrates but not of short peptide substrates is affected Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
N-acetyl-Val-Glu-Ile-Asp-aldehyde
-
 Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.02371
-
 N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin pH 7.5, 37°C, mutant enzyme R44K Homo sapiens
0.0277
-
 N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin pH 7.5, 37°, wild-type enzyme Homo sapiens
0.03063
-
 N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin pH 7.5, 37°C, mutant enzyme R42A/R43A/R44A Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens P55212
-
-

Purification (Commentary)

Purification (Comment) Organism
-
 Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
lamin c + H2O
-
 Homo sapiens ?
-
 ?
additional information stabilization of the N- and C-terminal loops by the tri-arginine patch is critical for the dynamics of caspase-6. This change in dynamics plays a key role in the mechanism by which the enzyme recognizes protein substrates Homo sapiens ?
-
 ?
N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin + H2O
-
 Homo sapiens N-acetyl-Val-Glu-Ile-Asp + 7-amino-4-methylcoumarin
-
 ?

Temperature Optimum [°C]

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

Temperature Stability [°C]

Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
65.8
-
 melting temperature, mutant enzyme R42A/R43A/R44A Homo sapiens
69.9
-
 melting temperature, mutant enzyme R44K Homo sapiens
73.8
-
 melting temperature, wild-type enzyme Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
1.39
-
 N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin pH 7.5, 37°C, mutant enzyme R44K Homo sapiens
1.59
-
 N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin pH 7.5, 37°, wild-type enzyme Homo sapiens
1.66
-
 N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin pH 7.5, 37°C, mutant enzyme R42A/R43A/R44A Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
 assay at Homo sapiens

General Information

General Information Comment Organism
physiological function an exosite tri-arginine patch, 42RRR44, located within the disordered N-terminal domain on caspase-6 is critical for protein substrate recognition and turnover and therefore highly relevant for diseases such as cancer in which caspase-6-mediated apoptosis is often disrupted, and in neurodegeneration in which caspase-6 plays a central role Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
51.9
-
 N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin pH 7.5, 37°C, mutant enzyme R44K Homo sapiens
54.7
-
 N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin pH 7.5, 37°C, mutant enzyme R42A/R43A/R44A Homo sapiens
58.3
-
 N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin pH 7.5, 37°, wild-type enzyme Homo sapiens