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Literature summary for 3.5.3.6 extracted from

  • Slade, D.J.; Fang, P.; Dreyton, C.J.; Zhang, Y.; Fuhrmann, J.; Rempel, D.; Bax, B.D.; Coonrod, S.A.; Lewis, H.D.; Guo, M.; Gross, M.L.; Thompson, P.R.
    Protein arginine deiminase 2 binds calcium in an ordered fashion implications for inhibitor design (2015), ACS Chem. Biol., 10, 1043-1053 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.5.3.6

Application

Application Comment Organism
drug development the enzyme is a particularly attractive therapeutic target for breast cancer because it is recruited by the estrogen receptor to endoplasmic reticulum target gene promoters where it citrullinates histone H3 at R26, leading to ER-target gene activation Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
-
 Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
sitting-drop vapor-diffusion technique at 23°C, apoPAD2 crystals with increasing concentrations of calcium (0-10 mM), 16 structures are solved at eight different calcium concentrations to 1.66-1.97 A Homo sapiens

Protein Variants

Protein Variants Comment Organism
D123N 2.5fold decrease in kcat/Km compared to wild-type value with N-alpha-benzoyl-L-arginine ethyl ester as substrate Homo sapiens
D125A 2.75fold decrease in kcat/Km compared to wild-type value with N-alpha-benzoyl-L-arginine ethyl ester as substrate Homo sapiens
D166A 85fold decrease in kcat/Km compared to wild-type value with N-alpha-benzoyl-L-arginine ethyl ester as substrate Homo sapiens
D169A 2fold decrease in kcat/Km compared to wild-type value with N-alpha-benzoyl-L-arginine ethyl ester as substrate Homo sapiens
D177A 15fold decrease in kcat/Km compared to wild-type value with N-alpha-benzoyl-L-arginine ethyl ester as substrate Homo sapiens
D370A 220fold decrease in kcat/Km compared to wild-type value with N-alpha-benzoyl-L-arginine ethyl ester as substrate Homo sapiens
D374A 145fold decrease in kcat/Km compared to wild-type value with N-alpha-benzoyl-L-arginine ethyl ester as substrate Homo sapiens
D389A 20fold decrease in kcat/Km compared to wild-type value with N-alpha-benzoyl-L-arginine ethyl ester as substrate Homo sapiens
E352A 1250fold decrease in kcat/Km compared to wild-type value with N-alpha-benzoyl-L-arginine ethyl ester as substrate Homo sapiens
E412A 3300fold decrease in kcat/Km compared to wild-type value with N-alpha-benzoyl-L-arginine ethyl ester as substrate Homo sapiens
F221A/F222A 1.1fold increase in kcat/Km compared to wild-type value with N-alpha-benzoyl-L-arginine ethyl ester as substrate Homo sapiens
Q350A 2350fold decrease in kcat/Km compared to wild-type value with N-alpha-benzoyl-L-arginine ethyl ester as substrate Homo sapiens
R347A fold decrease in kcat/Km compared to wild-type value with N-alpha-benzoyl-L-arginine ethyl ester as substrate Homo sapiens
W373A 50fold decrease in kcat/Km compared to wild-type value with N-alpha-benzoyl-L-arginine ethyl ester as substrate Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.1
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme F221A/F222A Homo sapiens
0.12
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D123N Homo sapiens
0.14
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D125A Homo sapiens
0.16
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, wild-type enzyme Homo sapiens
0.25
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D169A Homo sapiens
0.33
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D166A Homo sapiens
0.6
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D389A Homo sapiens
2.4
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D177A Homo sapiens
3.4
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme E352A Homo sapiens
4.4
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme R347 Homo sapiens
5
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D370A Homo sapiens
6.3
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme Q350A Homo sapiens
8
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D374A Homo sapiens
13
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme E412A Homo sapiens
30
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme W373A Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Ca2+ the concentration of calcium required for in vitro activity is at least 10 times higher than cellular calcium concentrations (i.e., 0.0001-0.010 mM). Calcium binding occurs in an ordered fashion. A calcium switch (calcium binding sites 3, 4, and 5) controls the overall calcium dependence of the enzyme Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9Y2J8
-
-

Purification (Commentary)

Purification (Comment) Organism
-
 Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
N-alpha-benzoyl-L-arginine ethyl ester + H2O
-
 Homo sapiens N-alpha-benzoyl-L-citrulline methyl ester + NH3
-
 ?

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.03
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme Q350A Homo sapiens
0.1
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme E412A Homo sapiens
0.2
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme W373A Homo sapiens
0.25
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme E352A Homo sapiens
0.35
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D166A Homo sapiens
0.51
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D389A Homo sapiens
0.6
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D370A Homo sapiens
0.8
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D123N Homo sapiens
0.8
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D125A Homo sapiens
1.53
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme R347 Homo sapiens
1.55
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D374A Homo sapiens
1.8
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D169A Homo sapiens
1.8
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme F221A/F222A Homo sapiens
2.65
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, wild-type enzyme Homo sapiens
2.65
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D177A Homo sapiens

General Information

General Information Comment Organism
malfunction calcium-dependent histone-modifying enzymes whose activity is dysregulated in inflammatory diseases and cancer Homo sapiens
metabolism protein arginine deiminases are calcium-dependent histone-modifying enzymes whose activity is dysregulated in inflammatory diseases and cancer. PAD2 functions as an estrogen receptor (ER) coactivator in breast cancer cells via the citrullination of histone tail arginine residues at ER binding sites Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.005
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme Q350A Homo sapiens
0.007
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme E412A Homo sapiens
0.007
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme W373A Homo sapiens
0.075
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme E352A Homo sapiens
0.115
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D370A Homo sapiens
0.195
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D374A Homo sapiens
0.35
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme R347 Homo sapiens
0.845
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D389A Homo sapiens
1.065
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D166A Homo sapiens
1.1
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D177A Homo sapiens
6
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D125A Homo sapiens
6.8
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D123N Homo sapiens
7.9
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme D169A Homo sapiens
16.5
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, wild-type enzyme Homo sapiens
18
-
 N-alpha-benzoyl-L-arginine ethyl ester pH 7.6, 37°C, mutant enzyme F221A/F222A Homo sapiens