Cytochrome P450 2C9 from Homo sapiens

Enzyme Description

Extremophile
No
EC Number

Sequence

Length: 490 amino acids
MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSKVYGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKKWKEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICSIIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFMKSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTETTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYIDLLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFKKSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVPPFYQLCFIPV
Vanessa GonzΓ‘lez-PΓ©rez et al. (2012) β€” Impact of Organic Solvents on Cytochrome P450 Probe Reactions: Filling the Gap with (S)-Warfarin and Midazolam Hydroxylation
Drug Metabolism and Disposition  Β· doi:10.1124/dmd.112.047134 β†—  Β· Activity - Classical
54 measurements
Database ID
UniProt: P11712 β†—
Sequence Annotation
Inferred - from protein name
Protein Source
Recombinant, host insect cells

Experimental Data (54 measurements)

54 measurements β€” page 1 of 3
Mutation Property Assay Solvent Solvent Volume Aqueous ReferenceWT Reference Measured Value Units Solution pH Temperature Substrate(s) Product(s) Cofactor(s) Shaking Comments
WT Activity - Classical Activity measured by HPLC-coupled mass spectrometry in the presence of organic solvent Acetonitrile 0.1% 100 β€” 76 % 100 mM potassium phosphate buffer 7.4 37Β°C 4 Β΅M (S)-Warfarin (S)-7-Hydroxywarfarin 1 mM NADPH β€” Classical aqueous control (in %)
WT Activity - Classical Activity measured by HPLC-coupled mass spectrometry in the presence of organic solvent Dimethyl Sulfoxide (DMSO) 2% 100 β€” 23 % 100 mM potassium phosphate buffer 7.4 37Β°C 4 Β΅M (S)-Warfarin (S)-7-Hydroxywarfarin 1 mM NADPH β€” Classical aqueous control (in %)
WT Activity - Classical Activity measured by HPLC-coupled mass spectrometry in the presence of organic solvent Dimethyl Sulfoxide (DMSO) 1% 100 β€” 41 % 100 mM potassium phosphate buffer 7.4 37Β°C 4 Β΅M (S)-Warfarin (S)-7-Hydroxywarfarin 1 mM NADPH β€” Classical aqueous control (in %)
WT Activity - Classical Activity measured by HPLC-coupled mass spectrometry in the presence of organic solvent Dimethyl Sulfoxide (DMSO) 0.1% 100 β€” 62 % 100 mM potassium phosphate buffer 7.4 37Β°C 4 Β΅M (S)-Warfarin (S)-7-Hydroxywarfarin 1 mM NADPH β€” Classical aqueous control (in %)
WT Activity - Classical Activity measured by HPLC-coupled mass spectrometry in the presence of organic solvent Acetone 0.1% 100 β€” 69 % 100 mM potassium phosphate buffer 7.4 37Β°C 4 Β΅M (S)-Warfarin (S)-7-Hydroxywarfarin 1 mM NADPH β€” Classical aqueous control (in %)
WT Activity - Classical Activity measured by HPLC-coupled mass spectrometry in the presence of organic solvent Ethanol 2% 100 β€” 5 % 100 mM potassium phosphate buffer 7.4 37Β°C 4 Β΅M (S)-Warfarin (S)-7-Hydroxywarfarin 1 mM NADPH β€” Classical aqueous control (in %)
WT Activity - Classical Activity measured by HPLC-coupled mass spectrometry in the presence of organic solvent Acetone 1% 100 β€” 42 % 100 mM potassium phosphate buffer 7.4 37Β°C 4 Β΅M (S)-Warfarin (S)-7-Hydroxywarfarin 1 mM NADPH β€” Classical aqueous control (in %)
WT Activity - Classical Activity measured by HPLC-coupled mass spectrometry in the presence of organic solvent Ethanol 1% 100 β€” 20 % 100 mM potassium phosphate buffer 7.4 37Β°C 4 Β΅M (S)-Warfarin (S)-7-Hydroxywarfarin 1 mM NADPH β€” Classical aqueous control (in %)
WT Activity - Classical Activity measured by HPLC-coupled mass spectrometry in the presence of organic solvent Ethanol 0.1% 100 β€” 59 % 100 mM potassium phosphate buffer 7.4 37Β°C 4 Β΅M (S)-Warfarin (S)-7-Hydroxywarfarin 1 mM NADPH β€” Classical aqueous control (in %)
WT Activity - Classical Activity measured by HPLC-coupled mass spectrometry in the presence of organic solvent Acetone 2% 100 β€” 22 % 100 mM potassium phosphate buffer 7.4 37Β°C 4 Β΅M (S)-Warfarin (S)-7-Hydroxywarfarin 1 mM NADPH β€” Classical aqueous control (in %)
WT Activity - Classical Activity measured by HPLC-coupled mass spectrometry in the presence of organic solvent Methanol 2% 100 β€” 18 % 100 mM potassium phosphate buffer 7.4 37Β°C 4 Β΅M (S)-Warfarin (S)-7-Hydroxywarfarin 1 mM NADPH β€” Classical aqueous control (in %)
WT Activity - Classical Activity measured by HPLC-coupled mass spectrometry in the presence of organic solvent Isopropanol 0.1% 100 β€” 47 % 100 mM potassium phosphate buffer 7.4 37Β°C 4 Β΅M (S)-Warfarin (S)-7-Hydroxywarfarin 1 mM NADPH β€” Classical aqueous control (in %)
WT Activity - Classical Activity measured by HPLC-coupled mass spectrometry in the presence of organic solvent Methanol 1% 100 β€” 49 % 100 mM potassium phosphate buffer 7.4 37Β°C 4 Β΅M (S)-Warfarin (S)-7-Hydroxywarfarin 1 mM NADPH β€” Classical aqueous control (in %)
WT Activity - Classical Activity measured by HPLC-coupled mass spectrometry in the presence of organic solvent Methanol 0.1% 100 β€” 79 % 100 mM potassium phosphate buffer 7.4 37Β°C 4 Β΅M (S)-Warfarin (S)-7-Hydroxywarfarin 1 mM NADPH β€” Classical aqueous control (in %)
WT Activity - Classical Activity measured by HPLC-coupled mass spectrometry in the presence of organic solvent Isopropanol 1% 100 β€” 14 % 100 mM potassium phosphate buffer 7.4 37Β°C 4 Β΅M (S)-Warfarin (S)-7-Hydroxywarfarin 1 mM NADPH β€” Classical aqueous control (in %)
WT Activity - Classical Activity measured by HPLC-coupled mass spectrometry in the presence of organic solvent Acetonitrile 1% 100 β€” 66 % 100 mM potassium phosphate buffer 7.4 37Β°C 4 Β΅M (S)-Warfarin (S)-7-Hydroxywarfarin 1 mM NADPH β€” Classical aqueous control (in %)
WT Activity - Classical Activity measured by HPLC-coupled mass spectrometry in the presence of organic solvent Isopropanol 2% 100 β€” 2 % 100 mM potassium phosphate buffer 7.4 37Β°C 4 Β΅M (S)-Warfarin (S)-7-Hydroxywarfarin 1 mM NADPH β€” Classical aqueous control (in %)
WT Activity - Classical Activity measured by HPLC-coupled mass spectrometry in the presence of organic solvent Acetonitrile 2% 100 β€” 62 % 100 mM potassium phosphate buffer 7.4 37Β°C 4 Β΅M (S)-Warfarin (S)-7-Hydroxywarfarin 1 mM NADPH β€” Classical aqueous control (in %)
I359L Activity - Classical Activity measured by HPLC-coupled mass spectrometry in the presence of organic solvent Isopropanol 2% 100 2 4 % 100 mM potassium phosphate buffer 7.4 37Β°C 4 Β΅M (S)-Warfarin (S)-7-Hydroxywarfarin 1 mM NADPH β€” Classical aqueous control (in %)
R144C Activity - Classical Activity measured by HPLC-coupled mass spectrometry in the presence of organic solvent Isopropanol 2% 100 2 2 % 100 mM potassium phosphate buffer 7.4 37Β°C 4 Β΅M (S)-Warfarin (S)-7-Hydroxywarfarin 1 mM NADPH β€” Classical aqueous control (in %)
β€Ή Prev
1 2 3

Mutations in this dataset (3)

WT R144C I359L

Visualization : Activity β€” Classical

One bar per measurement. Colour = solvent, shade = solvent volume. β€” β€” β€” Reference value. Hover for details.

Mutation Effect

Mutation impact on enzyme stability and function in the presence of organic solvent: comparison of wild-type and mutant values in identical conditions.

Structure

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