Cloned (Comment) | Organism |
---|---|
expression of His-tagged wild-type and mutant p38 isozyme alpha | Mus musculus |
Crystallization (Comment) | Organism |
---|---|
purified p38 isozyme alpha bound to several inhibitors pyridinyl imidazole-type inhibitors, X-ray diffraction structure determination and analysis at 2.1-2.5 A resolution | Mus musculus |
Protein Variants | Comment | Organism |
---|---|---|
G110A | site-directed mutagenesis of isozyme alpha, the mutant shows a slightly decreased Km value for ATP, but unaltered activity compared to the wild-type enzyme, decreased sensitivity for inhibitors compared to the wild-type enzyme | Mus musculus |
G110D | site-directed mutagenesis of isozyme alpha, the mutant shows a decreased Km value for ATP, but unaltered activity compared to the wild-type enzyme, decreased sensitivity for inhibitors compared to the wild-type enzyme | Mus musculus |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
1-(2,6-dichloro-phenyl)-5-(2,4-difluoro-phenyl)-7-piperazin-1-yl-3,4-dihydro-1H-quinazolin-2-one | highly selective for p38 isozyme alpha wild-type with IC50 of 3.2 nM, the IC50 for mutants G110A and G110D are 37 nM and 56 nM, respectively, no inhibition of JNK3, JNK2, and ERK | Mus musculus | |
1-(2,6-dichloro-phenyl)-5-(2,4-difluoro-phenyl)-7-piperidin-4-yl-3,4-dihydro-1H-quinolin-2-one | highly selective for p38 isozyme alpha wild-type with IC50 of 0.74 nM, the IC50 for mutants G110A and G110D are 26 nM and 67 nM, respectively, no inhibition of JNK3, JNK2, and ERK | Mus musculus | |
1-(2,6-dichloro-phenyl)-6-(2,4-difluoro-phenylsulfanyl)-7-(1,2,3,6-tetrahydro-pyridin-4-yl)-3,4-dihydro-1H-pyrido[3,2-d]pyrimidin-2-one | highly selective for p38 isozyme alpha wild-type with IC50 of 4.3 nM, the IC50 for mutants G110A and G110D are 61 nM and 160 nM, respectively, no inhibition of JNK3, JNK2, and ERK | Mus musculus | |
BIRB796 | binding structure with isozyme p38alpha | Mus musculus | |
additional information | structural basis for inhibitor selectivity for p38 over other MAPKs such as ERK or JNK, overview | Mus musculus | |
pyridinyl imidazole-type inhibitors | IC50 of 15-48 nM | Mus musculus | |
SB203580 | inhibits the p38 isozymes isozymes alpha, beta, and gamma | Mus musculus | |
VK19911 | - |
Mus musculus | |
VX745 | - |
Mus musculus | |
[4-[3-methyl-2-piperidin-4-yl-5-(3-trifluoromethyl-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl]-((S)-1-phenyl-ethyl)-amine | highly selective for p38 isozyme alpha wild-type and mutants with IC50 of 0.10-0.14 nM, IC50 for JNK2 is 680 nM, for JNK3 970 nM and for ERK 660 nM | Mus musculus |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.048 | - |
ATP | pH 7.0, 30°C, mutant G110D of p38 isozyme alpha | Mus musculus | |
0.085 | - |
ATP | pH 7.0, 30°C, mutant G110A of p38 isozyme alpha | Mus musculus | |
0.096 | - |
ATP | pH 7.0, 30°C, wild-type p38 isozyme alpha | Mus musculus |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | - |
Mus musculus |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Mus musculus | P47811 | isozymes alpha, beta, gamma, and delta of p38 | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + protein ATF2 | - |
Mus musculus | ADP + phosphorylated protein ATF2 | - |
? |
Synonyms | Comment | Organism |
---|---|---|
ERK | - |
Mus musculus |
JNK2 | - |
Mus musculus |
JNK3 | - |
Mus musculus |
p38alpha MAP kinase | - |
Mus musculus |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
30 | - |
assay at | Mus musculus |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7 | - |
assay at | Mus musculus |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Mus musculus |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0000001 | 0.00000014 | highly selective for p38 isozyme alpha wild-type and mutants with IC50 of 0.10-0.14 nM | Mus musculus | [4-[3-methyl-2-piperidin-4-yl-5-(3-trifluoromethyl-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl]-((S)-1-phenyl-ethyl)-amine | |
0.0000043 | - |
highly selective for p38 isozyme alpha wild-type with IC50 of 4.3 nM, respectively, no inhibition of JNK3, JNK2, and ERK | Mus musculus | 1-(2,6-dichloro-phenyl)-6-(2,4-difluoro-phenylsulfanyl)-7-(1,2,3,6-tetrahydro-pyridin-4-yl)-3,4-dihydro-1H-pyrido[3,2-d]pyrimidin-2-one | |
0.000015 | 0.000048 | IC50 of 15-48 nM | Mus musculus | pyridinyl imidazole-type inhibitors | |
0.000061 | - |
IC50 for mutant G110A 61 nM | Mus musculus | 1-(2,6-dichloro-phenyl)-6-(2,4-difluoro-phenylsulfanyl)-7-(1,2,3,6-tetrahydro-pyridin-4-yl)-3,4-dihydro-1H-pyrido[3,2-d]pyrimidin-2-one | |
0.00016 | - |
IC50 mutant G110D 160 nM, respectively, no inhibition of JNK3, JNK2, and ERK | Mus musculus | 1-(2,6-dichloro-phenyl)-6-(2,4-difluoro-phenylsulfanyl)-7-(1,2,3,6-tetrahydro-pyridin-4-yl)-3,4-dihydro-1H-pyrido[3,2-d]pyrimidin-2-one | |
0.00066 | - |
Ic50 for ERK 660 nM | Mus musculus | [4-[3-methyl-2-piperidin-4-yl-5-(3-trifluoromethyl-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl]-((S)-1-phenyl-ethyl)-amine | |
0.00068 | - |
IC50 for JNK2 is 680 nM | Mus musculus | [4-[3-methyl-2-piperidin-4-yl-5-(3-trifluoromethyl-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl]-((S)-1-phenyl-ethyl)-amine | |
0.00097 | - |
IC50 for JNK3 970 nM | Mus musculus | [4-[3-methyl-2-piperidin-4-yl-5-(3-trifluoromethyl-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl]-((S)-1-phenyl-ethyl)-amine |