Crystallization (Comment) | Organism |
---|---|
substrate docking on a homology model suggests possible interactions of ADP-ribose with seven residues located, with one exception (Cys253), either within the metallo-dependent phosphatases signature (Gln27, Asn110, His111), or in unique structural regions of the ADPRibase-Mn family: s2s3 (Phe37 and Arg43) and h7h8 (Phe210), around the active site entrance. Residue Phe37 is needed for ADP-ribose preference without catalytic effect. Arg43 is essential for catalysis. Cys253 is hindering for cADPR phosphohydrolase | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
C253A | mutant displays a tenfold increased efficiency for cADP-ribose, with no or modest effect on the other substrates | Homo sapiens |
F210A | lowers 40-70fold the catalytic efficiency for ADP-ribose, CDP-choline and 2',3'-cAMP hydrolysis, and 500fold for cADP-ribose | Homo sapiens |
F37A | 19fold increased Km for ADP-ribose, with only a 2-3fold increase of the CDP-choline and 2',3'-cAMP Km values | Homo sapiens |
F37A/L196A | mutation lessens the relative preference for ADP-ribose versus cADP-ribose | Homo sapiens |
F37A/L196F | mutation lessens the relative preference for ADP-ribose versus cADP-ribose | Homo sapiens |
F37A/L196F/C253A | cyclic ADP-ribose is the best substrate for the mutant | Homo sapiens |
F37Y | similar kinetic parameters as the wild type | Homo sapiens |
H111A | marked efficiency decrease with all substrates except 2',3'-cAMP | Homo sapiens |
H111N | marked efficiency decrease with all substrates except 2',3'-cAMP | Homo sapiens |
L196A | mutation causes only a modest 2-5fold decrease of catalytic efficiency with the four substrates tested | Homo sapiens |
N110A | 100-250fold reduction in catalytic efficiency for the hydrolysis of CDP-choline or 2',3'-cAMP | Homo sapiens |
Q27H | mutation reduces 11-13-fold the catalytic efficiency of the hydrolysis of ADP-ribose, CDP-choline or 2',3'-cAMP, and 27fold the hydrolysis of cADP-ribose | Homo sapiens |
R43A | drastic decrease of catalytic efficiency | Homo sapiens |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.06 | - |
ADP-ribose | wild-type, pH 7.5, 37°C | Homo sapiens | |
0.077 | - |
ADP-ribose | mutant F37Y, pH 7.5, 37°C | Homo sapiens | |
0.078 | - |
ADP-ribose | mutant H111N, pH 7.5, 37°C | Homo sapiens | |
0.094 | - |
ADP-ribose | mutant C253A, pH 7.5, 37°C | Homo sapiens | |
0.115 | - |
ADP-ribose | mutant R43A, pH 7.5, 37°C | Homo sapiens | |
0.13 | - |
ADP-ribose | mutant L196A, pH 7.5, 37°C | Homo sapiens | |
0.14 | - |
ADP-ribose | mutant H111A, pH 7.5, 37°C | Homo sapiens | |
0.2 | - |
cADP-ribose | mutant C253A, pH 7.5, 37°C | Homo sapiens | |
0.2 | - |
ADP-ribose | mutant Q27H, pH 7.5, 37°C | Homo sapiens | |
0.29 | - |
ADP-ribose | mutant N110A, pH 7.5, 37°C | Homo sapiens | |
0.35 | - |
CDP-choline | wild-type, pH 7.5, 37°C | Homo sapiens | |
0.43 | - |
CDP-choline | mutant F37Y, pH 7.5, 37°C | Homo sapiens | |
0.46 | - |
cADP-ribose | mutant F37A/L196F/C253A, pH 7.5, 37°C | Homo sapiens | |
0.47 | - |
CDP-choline | mutant L196A, pH 7.5, 37°C | Homo sapiens | |
0.5 | - |
CDP-choline | mutant C253A, pH 7.5, 37°C | Homo sapiens | |
0.78 | - |
cADP-ribose | wild-type, pH 7.5, 37°C | Homo sapiens | |
0.97 | - |
CDP-choline | mutant F37A, pH 7.5, 37°C | Homo sapiens | |
1.05 | - |
2',3'-cAMP | mutant N110A, pH 7.5, 37°C | Homo sapiens | |
1.15 | - |
ADP-ribose | mutant F37A, pH 7.5, 37°C | Homo sapiens | |
1.15 | - |
ADP-ribose | mutant F37A/L196A, pH 7.5, 37°C | Homo sapiens | |
1.2 | - |
ADP-ribose | mutant F37A/L196F/C253A, pH 7.5, 37°C | Homo sapiens | |
1.25 | - |
CDP-choline | mutant F37A/L196A, pH 7.5, 37°C | Homo sapiens | |
1.25 | - |
2',3'-cAMP | mutant H111A, pH 7.5, 37°C | Homo sapiens | |
1.5 | - |
CDP-choline | mutant F37A/L196F, pH 7.5, 37°C | Homo sapiens | |
1.6 | - |
ADP-ribose | mutant F37A/L196F, pH 7.5, 37°C | Homo sapiens | |
1.7 | - |
CDP-choline | mutant F37A/L196F/C253A, pH 7.5, 37°C | Homo sapiens | |
1.8 | - |
2',3'-cAMP | mutant H111N, pH 7.5, 37°C | Homo sapiens | |
2.1 | - |
ADP-ribose | mutant F210A, pH 7.5, 37°C | Homo sapiens | |
2.3 | - |
2',3'-cAMP | mutant Q27H, pH 7.5, 37°C | Homo sapiens | |
2.4 | - |
2',3'-cAMP | wild-type, pH 7.5, 37°C | Homo sapiens | |
2.5 | - |
2',3'-cAMP | mutant F37Y, pH 7.5, 37°C | Homo sapiens | |
2.6 | - |
2',3'-cAMP | mutant C253A, pH 7.5, 37°C | Homo sapiens | |
2.7 | - |
CDP-choline | mutant H111N, pH 7.5, 37°C | Homo sapiens | |
2.7 | - |
CDP-choline | mutant Q27H, pH 7.5, 37°C | Homo sapiens | |
3.4 | - |
2',3'-cAMP | mutant L196A, pH 7.5, 37°C | Homo sapiens | |
4 | - |
CDP-choline | mutant N110A, pH 7.5, 37°C | Homo sapiens | |
4.8 | - |
2',3'-cAMP | mutant F37A/L196A, pH 7.5, 37°C | Homo sapiens | |
5.1 | - |
2',3'-cAMP | mutant F37A, pH 7.5, 37°C | Homo sapiens | |
5.2 | - |
2',3'-cAMP | mutant F37A/L196F/C253A, pH 7.5, 37°C | Homo sapiens | |
7.1 | - |
2',3'-cAMP | mutant F37A/L196F, pH 7.5, 37°C | Homo sapiens | |
7.5 | - |
CDP-choline | mutant H111A, pH 7.5, 37°C | Homo sapiens | |
7.6 | - |
2',3'-cAMP | mutant F210A, pH 7.5, 37°C | Homo sapiens | |
7.6 | - |
2',3'-cAMP | mutant R43A, pH 7.5, 37°C | Homo sapiens | |
9 | - |
CDP-choline | mutant R43A, pH 7.5, 37°C | Homo sapiens | |
11 | - |
CDP-choline | mutant F210A, pH 7.5, 37°C | Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | W0NWJ0 | - |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
2',3'-cAMP + H2O | - |
Homo sapiens | 3'AMP | - |
? | |
ADP-ribose + H2O | - |
Homo sapiens | AMP + D-ribose 5-phosphate | - |
? | |
cADP-ribose + H2O | - |
Homo sapiens | N1-(5-phosphoribosyl)-AMP + phosphate | - |
? | |
CDP-choline + H2O | - |
Homo sapiens | CMP + choline phosphate | - |
? |
Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.003 | - |
ADP-ribose | mutant R43A, pH 7.5, 37°C | Homo sapiens | |
0.025 | - |
CDP-choline | mutant R43A, pH 7.5, 37°C | Homo sapiens | |
0.11 | - |
2',3'-cAMP | mutant N110A, pH 7.5, 37°C | Homo sapiens | |
0.47 | - |
ADP-ribose | mutant H111A, pH 7.5, 37°C | Homo sapiens | |
0.95 | - |
2',3'-cAMP | mutant R43A, pH 7.5, 37°C | Homo sapiens | |
2 | 8 | 2',3'-cAMP | mutant F37A/L196F, pH 7.5, 37°C | Homo sapiens | |
2.2 | - |
CDP-choline | mutant H111A, pH 7.5, 37°C | Homo sapiens | |
2.3 | - |
ADP-ribose | mutant H111N, pH 7.5, 37°C | Homo sapiens | |
2.7 | - |
2',3'-cAMP | mutant F210A, pH 7.5, 37°C | Homo sapiens | |
3 | 6 | 2',3'-cAMP | mutant F37A, pH 7.5, 37°C | Homo sapiens | |
3.2 | - |
cADP-ribose | wild-type, pH 7.5, 37°C | Homo sapiens | |
4.3 | - |
ADP-ribose | mutant N110A, pH 7.5, 37°C | Homo sapiens | |
4.3 | - |
2',3'-cAMP | mutant Q27H, pH 7.5, 37°C | Homo sapiens | |
5.3 | - |
CDP-choline | mutant H111N, pH 7.5, 37°C | Homo sapiens | |
5.7 | - |
CDP-choline | mutant N110A, pH 7.5, 37°C | Homo sapiens | |
7 | - |
ADP-ribose | mutant F37A/L196A, pH 7.5, 37°C | Homo sapiens | |
7.4 | - |
2',3'-cAMP | mutant H111A, pH 7.5, 37°C | Homo sapiens | |
8 | - |
ADP-ribose | mutant F37A/L196F, pH 7.5, 37°C | Homo sapiens | |
8.9 | - |
cADP-ribose | mutant C253A, pH 7.5, 37°C | Homo sapiens | |
10 | - |
ADP-ribose | mutant Q27H, pH 7.5, 37°C | Homo sapiens | |
13 | - |
ADP-ribose | mutant F37A/L196F/C253A, pH 7.5, 37°C | Homo sapiens | |
14 | - |
ADP-ribose | mutant F37A, pH 7.5, 37°C | Homo sapiens | |
16 | - |
cADP-ribose | mutant F37A/L196F/C253A, pH 7.5, 37°C | Homo sapiens | |
16 | - |
ADP-ribose | mutant L196A, pH 7.5, 37°C | Homo sapiens | |
19 | - |
ADP-ribose | mutant F210A, pH 7.5, 37°C | Homo sapiens | |
19 | - |
2',3'-cAMP | mutant F37A/L196A, pH 7.5, 37°C | Homo sapiens | |
20 | - |
2',3'-cAMP | mutant F37A/L196F/C253A, pH 7.5, 37°C | Homo sapiens | |
25 | - |
CDP-choline | mutant F37A/L196A, pH 7.5, 37°C | Homo sapiens | |
26 | - |
CDP-choline | mutant F37A/L196F, pH 7.5, 37°C | Homo sapiens | |
29 | - |
CDP-choline | mutant L196A, pH 7.5, 37°C | Homo sapiens | |
30 | - |
2',3'-cAMP | mutant L196A, pH 7.5, 37°C | Homo sapiens | |
33 | - |
CDP-choline | mutant F37A, pH 7.5, 37°C | Homo sapiens | |
34 | - |
2',3'-cAMP | mutant H111N, pH 7.5, 37°C | Homo sapiens | |
35 | - |
ADP-ribose | wild-type, pH 7.5, 37°C | Homo sapiens | |
37 | - |
CDP-choline | mutant F37A/L196F/C253A, pH 7.5, 37°C | Homo sapiens | |
39 | - |
CDP-choline | mutant Q27H, pH 7.5, 37°C | Homo sapiens | |
50 | - |
CDP-choline | wild-type, pH 7.5, 37°C | Homo sapiens | |
50 | - |
CDP-choline | mutant F210A, pH 7.5, 37°C | Homo sapiens | |
50 | - |
ADP-ribose | mutant F37Y, pH 7.5, 37°C | Homo sapiens | |
60 | - |
2',3'-cAMP | wild-type, pH 7.5, 37°C | Homo sapiens | |
70 | - |
2',3'-cAMP | mutant F37Y, pH 7.5, 37°C | Homo sapiens | |
76 | - |
CDP-choline | mutant F37Y, pH 7.5, 37°C | Homo sapiens | |
79 | - |
CDP-choline | mutant C253A, pH 7.5, 37°C | Homo sapiens | |
83 | - |
2',3'-cAMP | mutant C253A, pH 7.5, 37°C | Homo sapiens | |
97 | - |
ADP-ribose | mutant C253A, pH 7.5, 37°C | Homo sapiens |
kcat/KM Value [1/mMs-1] | kcat/KM Value Maximum [1/mMs-1] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0001 | - |
cADP-ribose | mutant R43A, pH 7.5, 37°C | Homo sapiens | |
0.006 | - |
CDP-choline | mutant R43A, pH 7.5, 37°C | Homo sapiens | |
0.008 | - |
cADP-ribose | mutant F210A, pH 7.5, 37°C | Homo sapiens | |
0.03 | - |
ADP-ribose | mutant R43A, pH 7.5, 37°C | Homo sapiens | |
0.07 | - |
cADP-ribose | mutant H111A, pH 7.5, 37°C | Homo sapiens | |
0.1 | - |
2',3'-cAMP | mutant N110A, pH 7.5, 37°C | Homo sapiens | |
0.13 | - |
cADP-ribose | mutant N110A, pH 7.5, 37°C | Homo sapiens | |
0.13 | - |
2',3'-cAMP | mutant R43A, pH 7.5, 37°C | Homo sapiens | |
0.15 | - |
cADP-ribose | mutant Q27H, pH 7.5, 37°C | Homo sapiens | |
0.29 | - |
cADP-ribose | mutant H111N, pH 7.5, 37°C | Homo sapiens | |
0.3 | - |
CDP-choline | mutant H111A, pH 7.5, 37°C | Homo sapiens | |
0.4 | - |
2',3'-cAMP | mutant F210A, pH 7.5, 37°C | Homo sapiens | |
0.9 | - |
cADP-ribose | mutant F37A/L196A, pH 7.5, 37°C | Homo sapiens | |
0.9 | - |
cADP-ribose | mutant L196A, pH 7.5, 37°C | Homo sapiens | |
1.3 | - |
cADP-ribose | mutant F37A, pH 7.5, 37°C | Homo sapiens | |
1.5 | - |
CDP-choline | mutant N110A, pH 7.5, 37°C | Homo sapiens | |
1.6 | - |
cADP-ribose | mutant F37A/L196F, pH 7.5, 37°C | Homo sapiens | |
1.9 | - |
2',3'-cAMP | mutant Q27H, pH 7.5, 37°C | Homo sapiens | |
2 | - |
CDP-choline | mutant H111N, pH 7.5, 37°C | Homo sapiens | |
3 | - |
ADP-ribose | mutant H111A, pH 7.5, 37°C | Homo sapiens | |
3.9 | - |
2',3'-cAMP | mutant F37A/L196F, pH 7.5, 37°C | Homo sapiens | |
4 | - |
cADP-ribose | wild-type, pH 7.5, 37°C | Homo sapiens | |
4 | - |
CDP-choline | mutant F210A, pH 7.5, 37°C | Homo sapiens | |
4 | - |
2',3'-cAMP | mutant F37A/L196A, pH 7.5, 37°C | Homo sapiens | |
4 | - |
2',3'-cAMP | mutant F37A/L196F/C253A, pH 7.5, 37°C | Homo sapiens | |
4.1 | - |
cADP-ribose | mutant F37Y, pH 7.5, 37°C | Homo sapiens | |
4.8 | - |
ADP-ribose | mutant F37A/L196F, pH 7.5, 37°C | Homo sapiens | |
6 | - |
ADP-ribose | mutant F37A/L196A, pH 7.5, 37°C | Homo sapiens | |
6 | - |
2',3'-cAMP | mutant H111A, pH 7.5, 37°C | Homo sapiens | |
7 | - |
2',3'-cAMP | mutant F37A, pH 7.5, 37°C | Homo sapiens | |
9 | - |
ADP-ribose | mutant F210A, pH 7.5, 37°C | Homo sapiens | |
9 | - |
2',3'-cAMP | mutant L196A, pH 7.5, 37°C | Homo sapiens | |
11 | - |
ADP-ribose | mutant F37A/L196F/C253A, pH 7.5, 37°C | Homo sapiens | |
12 | - |
ADP-ribose | mutant F37A, pH 7.5, 37°C | Homo sapiens | |
14 | - |
CDP-choline | mutant Q27H, pH 7.5, 37°C | Homo sapiens | |
15 | - |
ADP-ribose | mutant N110A, pH 7.5, 37°C | Homo sapiens | |
17 | - |
CDP-choline | mutant F37A/L196F, pH 7.5, 37°C | Homo sapiens | |
19 | - |
2',3'-cAMP | mutant H111N, pH 7.5, 37°C | Homo sapiens | |
21 | - |
CDP-choline | mutant F37A/L196A, pH 7.5, 37°C | Homo sapiens | |
22 | - |
CDP-choline | mutant F37A/L196F/C253A, pH 7.5, 37°C | Homo sapiens | |
25 | - |
2',3'-cAMP | wild-type, pH 7.5, 37°C | Homo sapiens | |
28 | - |
2',3'-cAMP | mutant F37Y, pH 7.5, 37°C | Homo sapiens | |
29 | - |
ADP-ribose | mutant H111N, pH 7.5, 37°C | Homo sapiens | |
32 | - |
2',3'-cAMP | mutant C253A, pH 7.5, 37°C | Homo sapiens | |
34 | - |
CDP-choline | mutant F37A, pH 7.5, 37°C | Homo sapiens | |
35.5 | - |
cADP-ribose | mutant F37A/L196F/C253A, pH 7.5, 37°C | Homo sapiens | |
44 | - |
cADP-ribose | mutant C253A, pH 7.5, 37°C | Homo sapiens | |
52 | - |
ADP-ribose | mutant Q27H, pH 7.5, 37°C | Homo sapiens | |
62 | - |
CDP-choline | mutant L196A, pH 7.5, 37°C | Homo sapiens | |
120 | - |
ADP-ribose | mutant L196A, pH 7.5, 37°C | Homo sapiens | |
150 | - |
CDP-choline | wild-type, pH 7.5, 37°C | Homo sapiens | |
160 | - |
CDP-choline | mutant C253A, pH 7.5, 37°C | Homo sapiens | |
180 | - |
CDP-choline | mutant F37Y, pH 7.5, 37°C | Homo sapiens | |
590 | - |
ADP-ribose | wild-type, pH 7.5, 37°C | Homo sapiens | |
650 | - |
ADP-ribose | mutant F37Y, pH 7.5, 37°C | Homo sapiens | |
1000 | - |
ADP-ribose | mutant C253A, pH 7.5, 37°C | Homo sapiens |