Torpedo_number Report for: 288

aedae-ACHE

Mutation	Type	Evaluation system	Effect	Reference
F350Y	sdm	OP-resistance	OP-resistance Not yet found in nature	Vaughan_1997_Exp.Parasitol_87_237
F105S/ F350Y	sdm	Site directed mutagenesis	OP-resistance Not yet found in nature	Vaughan_1997_Exp.Parasitol_87_237
G285A/ F350Y	sdm	OP-resistance	OP-resistance Not yet found in nature	Vaughan_1997_Exp.Parasitol_87_237
F105S/ G285A/ F350Y	sdm	OP-resistance	OP-resistance Not yet found in nature	Vaughan_1997_Exp.Parasitol_87_237

brafl-ACHE2

Mutation	Type	Evaluation system	Reference
C310A	sdm	Inactivation by sulfhydryl	Pezzementi_2006_Invert.Neurosci_6_47
C310A/ C466A	sdm	Inactivation by sulfhydryl	Pezzementi_2006_Invert.Neurosci_6_47
C310A/ F312I	sdm	Inactivation by sulfhydryl	Pezzementi_2006_Invert.Neurosci_6_47

drome-ACHE

Mutation	Type	Evaluation system	Effect	Reference
L366A	sdm	Insecticide sensitivity		Boublik_2002_Protein.Eng_15_43
L366F	sdm	Insecticide sensitivity		Boublik_2002_Protein.Eng_15_43
L366F	sdm	Binding of Triton X-100 studies	mutation mimic the torpedo enzyme, no effect	Marcel_2000_J.Biol.Chem_275_11603

human-ACHE : (kinetic parameters)

Mutation	Kin.	Type	Evaluation system	Effect	Reference
F295L/ Y337A		sdm	Oxime interaction		Cochran_2011_J.Biol.Chem_286_29718
E202Q/ F295L/ Y337A		sdm	Oxime interaction		Cochran_2011_J.Biol.Chem_286_29718
F295L/ Y337A/ F338A		sdm	Oxime interaction		Cochran_2011_J.Biol.Chem_286_29718
F295S/ F338A		sdm	Acyl specificity	Acyl pocket 800-fold decreased catalytic activity, orientation of His 447	Shafferman_2005_Chem.Biol.Interact_157-158_123
F295T/ F338A		sdm	Acyl specificity	Acyl pocket 3400-fold decreased catalytic activity, orientation of His 447	Shafferman_2005_Chem.Biol.Interact_157-158_123
F295N/ F338A		sdm	Acyl specificity	Acyl pocket 110-fold decreased catalytic activity, orientation of His 447	Shafferman_2005_Chem.Biol.Interact_157-158_123
F295M/ F338A		sdm	Acyl specificity	Acyl pocket Only 6-fold decreased catalytic activity, orientation of His 447	Shafferman_2005_Chem.Biol.Interact_157-158_123
F295V/ F338A		sdm	Acyl specificity	Acyl pocket 380-fold decreased catalytic activity, orientation of His 447	Shafferman_2005_Chem.Biol.Interact_157-158_123
F295I/ F338A		sdm	Acyl specificity	Acyl pocket 1130-fold decreased catalytic activity, orientation of His 447	Shafferman_2005_Chem.Biol.Interact_157-158_123
F295L/ F338A		sdm	Acyl specificity	Acyl pocket 55-fold decreased catalytic activity, orientation of His 447	Shafferman_2005_Chem.Biol.Interact_157-158_123
F295L/ F338A		sdm	Oxime interaction		Cochran_2011_J.Biol.Chem_286_29718
F295L/ F297V	kin	sdm	Acyl specificity	Acyl pocket, Increases hydrolysis of BTC	Ordentlich_1993_J.Biol.Chem_268_17083, Shafferman_1993_Proc.Med.Def.Biosci.Rev_3_1097, Ashani_1994_Mol.Pharmacol_45_555
F295L/ F297V	kin	sdm	OP-specificity	increases reactivity towards DFP DEFP and paraoxon	Ordentlich_1996_J.Biol.Chem_271_11953'
F295L/ F297V	kin	sdm	OP-specificity	decrease in stereoselectivity	Ordentlich_2004_Biochemistry_43_11255
F295L/ F297V	kin	sdm	Acyl specificity	replacement of aromatic active center residues in human-ACHE by the corresponding residues in human-BCHE	Kaplan_2001_Biochemistry_40_7433
F295L/ F297V/ Y337A	kin	sdm	Acyl specificity	replacement of aromatic active center residues in human-ACHE by the corresponding residues in human-BCHE	Kaplan_2001_Biochemistry_40_7433, Barak_2005_Chem.Biol.Interact_157-158_219
Y72N/ Y124Q/ W286A/ F295L/ F297W/ Y337A		sdm	Acyl specificity	replacement of aromatic active center residues in human-ACHE by the corresponding residues in human-BCHE	Kaplan_2001_Biochemistry_40_7433
F295A/ F338A		sdm	Acyl specificity	Acyl pocket 680-fold decreased catalytic activity, orientation of His 447	Barak_2002_Biochemistry_41_8245, Shafferman_2005_Chem.Biol.Interact_157-158_123, Barak_2005_Chem.Biol.Interact_157-158_219
F295A/ F338A/ V407F		sdm	Acyl specificity	Acyl pocket only 3-fold decreased catalytic activity compensate F295A/F338A	Barak_2002_Biochemistry_41_8245, Barak_2005_Chem.Biol.Interact_157-158_219
Y72N/ Y124Q/ W286A/ F295L/ F297V/ Y337A/ V407F		sdm	Acyl specificity	Acyl pocket V407F does not increase kcat of the hexamutant	Barak_2002_Biochemistry_41_8245
F295A/ F297A		sdm	Acyl specificity	VX stereospecificity decrease in stereoselectivity	Ordentlich_2005_Chem.Biol.Interact_157-158_191
F295A	kin	sdm	Acyl specificity	Acyl pocket, OP-specificity.inhanced affinity for BTC	Ordentlich_1993_J.Biol.Chem_268_17083, Shafferman_1993_Proc.Med.Def.Biosci.Rev_3_1097, Ashani_1994_Mol.Pharmacol_45_555, Barak_1994_J.Biol.Chem_269_6296, Ordentlich_1995_5th.ChE.Meeting.Madras__221, Shafferman_1995_5th.ChE.Meeting.Madras__189
F295A	kin	sdm	OP-specificity	increased reactivity to DFP DEFP and paraoxon	Shafferman_1993_Proc.Med.Def.Biosci.Rev_3_1097, Ashani_1994_Mol.Pharmacol_45_555, Barak_1994_J.Biol.Chem_269_6296, Ordentlich_1995_5th.ChE.Meeting.Madras__221, Shafferman_1995_5th.ChE.Meeting.Madras__189, Ordentlich_1996_J.Biol.Chem_271_11953
F295A	kin	sdm	Acyl specificity	Acyl pocket, decreased catalytic activity, orientation of His 447	Barak_2002_Biochemistry_41_8245
F295A	kin	sdm	VX stereospecificity	decrease in stereoselectivity	Ordentlich_2004_Biochemistry_43_11255, Ordentlich_2005_Chem.Biol.Interact_157-158_191
F295L	kin	sdm	Acyl specificity	Acyl pocket, Increases hydrolysis of BTC less effect than F295A	Ordentlich_1993_J.Biol.Chem_268_17083, Shafferman_1993_Proc.Med.Def.Biosci.Rev_3_1097
F295L	kin	sdm	OP-specificity	increases reactivity towards DFP DEFP and paraoxon	Ordentlich_1996_J.Biol.Chem_271_11953'
F295L	kin	sdm	Oxime interaction		Cochran_2011_J.Biol.Chem_286_29718
F295L	kin	sdm	Acyl specificity	replacement of aromatic active center residues in human-ACHE by the corresponding residues in human-BCHE	Kaplan_2001_Biochemistry_40_7433
Y72N/ Y124Q/ W286A/ F295L/ F297V/ Y337A	kin	sdm	Acyl specificity	replacement of aromatic active center residues in human-ACHE by the corresponding residues in human-BCHE	Kaplan_2001_Biochemistry_40_7433

human-BCHE : (kinetic parameters)

Mutation	Kin.	Type	Evaluation system	Effect	Reference
A199S/ S287G/ A328W/ Y332G/ L286I		sdm	Cocaine hydrolysis	E10	Zheng_2010_Biochemistry_49_9113
T284Q/ P285S/ L286I/ S287H/ V288I		sdm	Search for phosphotriesterase activity		Terekhov_2017_Proc.Natl.Acad.Sci.U.S.A_114_2550
T284P/ P285S/ L286H/ V288G		sdm	Search for phosphotriesterase activity		Terekhov_2017_Proc.Natl.Acad.Sci.U.S.A_114_2550
T284N/ P285H/ L286I/ V288G		sdm	Search for phosphotriesterase activity		Terekhov_2017_Proc.Natl.Acad.Sci.U.S.A_114_2550
T284H/ P285T/ L286I/ S287H/ V288G		sdm	Search for phosphotriesterase activity		Terekhov_2017_Proc.Natl.Acad.Sci.U.S.A_114_2550
T284N/ P285K/ L286S/ S287N		sdm	Search for phosphotriesterase activity		Terekhov_2017_Proc.Natl.Acad.Sci.U.S.A_114_2550
L286H		sdm	Search for phosphotriesterase activity	Phosphotriesterase activity Identical to WT	Lockridge_1997_Biochemistry_36_786
L286H		sdm	Search for phosphotriesterase activity	Phosphotriesterase activity OP sensitive	Schopfer_2004_J.Med.Chem.Biol.Radiol.Def_2_1
L286K	kin	sdm	Acyl specificity	Acyl pocket, Km X 11 for BTC IC50 high increase for echothiophate and iso-OMPA	Gnatt_1994_J.Neurochem_62_749
L286Q	kin	sdm	Acyl specificity	Acyl pocket, Km X 9 for BTC IC50 high increase for echothiophate and iso-OMPA	Gnatt_1994_J.Neurochem_62_749
L286R	kin	sdm	Acyl specificity	Acyl pocket, low activity km X 5 for BTC	Gnatt_1994_J.Neurochem_62_749
L286R	kin	sdm	Acyl specificity	Acyl pocket, low activity km X 20 to 50 for ATC PTC BTC and BzCH	Boeck_2002_Biochem.Pharmacol_63_2101
L286R	kin	sdm	Acyl specificity	Acyl pocket R286 responsible for resistance to inhibition by Triton X-100	Boeck_2002_Biochem.Pharmacol_63_2101
L286R	kin	sdm	Binding of Triton X-100 studies	Acyl pocket R286 responsible for resistance to inhibition by Triton X-100	Boeck_2002_Biochem.Pharmacol_63_2101
L286D	kin	sdm	Acyl specificity	Acyl pocket, Km X 4 for BTC	Gnatt_1994_J.Neurochem_62_749

mouse-ACHE : (kinetic parameters)

Mutation	Kin.	Type	Evaluation system	Effect	Reference
F295A	kin	sdm	Acyl specificity	Acyl pocket specificity of chiral inhibitors	Hosea_1995_Biochemistry_34_11528
F295L	kin	sdm	Acyl specificity	Acyl pocket, confers butyrylcholinesterase activity	Vellom_1993_Biochemistry_32_12, Pickering_1995_5th.ChE.Meeting.Madras__227
F295L	kin	sdm	Fasciculin inhibition	low effect	Radic_1994_J.Biol.Chem_269_11233
F295L	kin	sdm	Aricept~Donepezil~E2020 inhibition	increase Ki vs WT	Saxena_2003_Eur.J.Biochem_270_4447
F295L	kin	sdm	Oxime interaction	enlargement of the active site of the gorge	Kovarik_2006_Biochem.Biophys.Res.Commun_342_973, Kovarik_2007_Toxicology_233_79
F295Y	kin	sdm	Acyl specificity	Acyl pocket decreases km and kcat for ACT	Radic_1993_Biochemistry_32_12074, Pickering_1995_5th.ChE.Meeting.Madras__227
F295L/ F297I	kin	sdm	Acyl specificity	Acyl pocket, reduced catalytic activity for ACT and enhanced for BCT	Vellom_1993_Biochemistry_32_12
F295L/ R296S/ F297I		sdm	Acyl specificity	Acyl pocket reduced catalytic activity for ACT and enhanced for BCT	Vellom_1993_Biochemistry_32_12
F295L/ Y337A		sdm	Oxime interaction	enlargement of the active site of the gorge	Kovarik_2006_Biochem.Biophys.Res.Commun_342_973, Kovarik_2007_Toxicology_233_79
F295L/ Y337A		sdm	Acyl specificity	enlargement of the active site of the gorge	Kovarik_2006_Biochem.Biophys.Res.Commun_342_973, Kovarik_2007_Toxicology_233_79
F295L/ Y337A		sdm	Oxime interaction		Kovarik_2004_Biochemistry_43_3222
F295L/ F297I/ Y337A		sdm	oxime interaction	enlargement of the active site of the gorge	Kovarik_2006_Biochem.Biophys.Res.Commun_342_973
F295L/ F297I/ Y337A		sdm	Oxime interaction		Kovarik_2004_Biochemistry_43_3222

nipbr-ACHEB

Mutation	Type	Evaluation system	Reference
M301A	sdm	Insecticide sensitivity	Schulze_2005_Anal.Chem_77_5823
M301A/ F345A	sdm	Insecticide sensitivity	Schulze_2005_Anal.Chem_77_5823
M301A/ F345Y	sdm	Insecticide sensitivity	Schulze_2005_Anal.Chem_77_5823
M301A/ W303A	sdm	Insecticide sensitivity	Schulze_2005_Anal.Chem_77_5823
M301A/ W303L	sdm	Insecticide sensitivity	Schulze_2005_Anal.Chem_77_5823

ratno-ACHE

Mutation	Kin.	Type	Evaluation system	Effect	Reference
F295L		sdm	Acyl specificity	less specific more inhibition by OP and Carbamates	Pleiss_1999_J.Mol.Catal.B.Enzym_6_287

ratno-BCHE

Mutation	Type	Evaluation system	Effect	Reference
R286L	sdm	Binding of Triton X-100 studies	R286 responsible for resistance to inhibition by Triton X-100	Boeck_2002_Biochem.Pharmacol_63_2101
R286L	sdm	Acyl pocket	R286 responsible for resistance to inhibition by Triton X-100	Boeck_2002_Biochem.Pharmacol_63_2101
R286L	sdm	Acyl specificity	Acyl pocket, no substantial reduction of Km for + charged substrates	Boeck_2002_Biochem.Pharmacol_63_2101

torma-ACHE

Mutation	Kin.	Type	Evaluation system	Effect	Reference
F288L/ F290V		sdm	Acyl specificity	Acyl pocket hydrolysis of BTC as well as ATC , inhibited also by iso-OMPA	Harel_1992_Proc.Natl.Acad.Sci.U.S.A_89_10827

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