Torpedo_number Report for: 72

drome-ACHE

Mutation	Type	Evaluation system	Effect	Reference
Y109A	sdm	Insecticide sensitivity		Boublik_2002_Protein.Eng_15_43
Y109D	sdm	Peripheral Anionic Site	changes conformation of catalytic site	Mutero_1992_Neuroreport_3_39
Y109D	sdm	Binding of Triton X-100 studies	mimic the torpedo enzyme, no effect	Marcel_2000_J.Biol.Chem_275_11603
Y109G	sdm	Peripheral Anionic Site	changes conformation of catalytic site	Mutero_1992_Neuroreport_3_39
Y109K	sdm	Peripheral Anionic Site	changes conformation of catalytic site	Mutero_1992_Neuroreport_3_39
Y109K	sdm	Binding of Triton X-100 studies	slightly decreases affinity for Triton	Marcel_2000_J.Biol.Chem_275_11603

human-ACHE : (kinetic parameters)

Mutation	Kin.	Type	Evaluation system	Effect	Reference
D74N	kin	sdm	Omega loop	No effect	Velan_1996_FEBS.Lett_395_22
D74N	kin	sdm	Peripheral Anionic Site	Affects conformation of active site and PAS	Shafferman_1992_EMBO.J_11_3561, Shafferman_1992_4th.ChE.Meeting.Eilat__165, Shafferman_1993_Proc.Med.Def.Biosci.Rev_3_1097, Shafferman_1995_5th.ChE.Meeting.Madras__189, Shafferman_1996_Biochem.J_318_833
D74N	kin	sdm	Substrate inhibition	Signal transduction Affects conformation of active site and PAS	Shafferman_1992_EMBO.J_11_3561, Shafferman_1992_4th.ChE.Meeting.Eilat__165, Shafferman_1993_Proc.Med.Def.Biosci.Rev_3_1097, Shafferman_1995_5th.ChE.Meeting.Madras__189, Shafferman_1996_Biochem.J_318_833
D74N	kin	sdm	Heat and pressure stability	strengthened heat or pressure stability	Clery-Barraud_2002_Eur.J.Biochem_269_4297
D74N	kin	sdm	VX stereospecificity	decrease in stereoselectivity	Ordentlich_2004_Biochemistry_43_11255, Ordentlich_2005_Chem.Biol.Interact_157-158_191
D74N	kin	sdm	oxime interaction	reactivation of tabun-inhibited human AChE. Rate constant 20-fold decreased for K027 and HLo-7. Unable to facilitate HI-6-mediated reactivation of tabun-hAChE	Artursson_2009_Toxicology_265_108
D74K	kin	sdm	Peripheral Anionic Site	Peripheral Anionic Site/signal transduction/allosteric modulation/substrate inhibition. Affects conformation of active site and PAS	Shafferman_1992_EMBO.J_11_3561, Shafferman_1992_4th.ChE.Meeting.Eilat__165
D74K	kin	sdm	Signal transduction	Affects conformation of active site and PAS	Shafferman_1992_EMBO.J_11_3561, Shafferman_1992_4th.ChE.Meeting.Eilat__165
D74G	kin	sdm	Peripheral Anionic Site	Peripheral Anionic Site/signal transduction/allosteric modulation/substrate inhibition. Affects conformation of active site and PAS	Shafferman_1992_EMBO.J_11_3561, Shafferman_1992_4th.ChE.Meeting.Eilat__165
D74G	kin	sdm	Signal transduction	Affects conformation of active site and PAS	Shafferman_1992_EMBO.J_11_3561, Shafferman_1992_4th.ChE.Meeting.Eilat__165
D74E	kin	sdm	Peripheral Anionic Site	Peripheral Anionic Site/signal transduction/allosteric modulation. Affects conformation of active site and PAS	Shafferman_1992_EMBO.J_11_3561, Shafferman_1992_4th.ChE.Meeting.Eilat__165
D74E	kin	sdm	Signal transduction	Affects conformation of active site and PAS	Shafferman_1992_EMBO.J_11_3561, Shafferman_1992_4th.ChE.Meeting.Eilat__165
D74E	kin	sdm	VX stereospecificity	no effect in stereoselectivity	Ordentlich_2005_Chem.Biol.Interact_157-158_191
D74E	kin	sdm	oxime interaction	reactivation of tabun-inhibited human AChE. Unable to facilitate HI-6-mediated reactivation of tabun-hAChE	Artursson_2009_Toxicology_265_108
D74N/ W286A		sdm	Peripheral Anionic Site	cooperativity of mutations D74 W286 10+4 increase Ki	Shafferman_1995_5th.ChE.Meeting.Madras__189
D74N/ Y341A		sdm	Peripheral Anionic Site	no cooperativity D74 Y341	Shafferman_1995_5th.ChE.Meeting.Madras__189
D74N/ W286A/ Y341A		sdm	Peripheral Anionic Site	cooperativity of mutations on D74 W286 for bisquaternary PAS inhib	Shafferman_1995_5th.ChE.Meeting.Madras__189

human-BCHE : (kinetic parameters)

Mutation	Kin.	Type	Evaluation system	Effect	Reference
D70H		nat	Peripheral anionic site	Natural variant Higher Km for charged substrates	Boeck_2002_Ann.Clin.Biochem_39_154
D70G	kin	sdm, nat	Succinylthiocholine binding	Higher Km for charged substrates	Masson_1997_Biochemistry_36_2266
D70G	kin	sdm, nat	Peripheral Anionic Site	Higher Km for substrates	Loewenstein-Lichtenstein_1996_Mol.Pharmacol_50_1423
D70G	kin	sdm, nat	Succinylcholine hydrolysis	Low hydrolysis	McGuire_1989_Proc.Natl.Acad.Sci.U.S.A_86_953, Neville_1990_J.Neurosci.Res_27_452, Neville_1992_EMBO.J_11_1641, Ehrlich_1994_Genomics_22_288, Masson_1995_5th.ChE.Meeting.Madras__230
D70G	kin	sdm, nat	Atypical variant	Low hydrolysis	McGuire_1989_Proc.Natl.Acad.Sci.U.S.A_86_953, Neville_1990_J.Neurosci.Res_27_452, Neville_1992_EMBO.J_11_1641, Ehrlich_1994_Genomics_22_288, Masson_1995_5th.ChE.Meeting.Madras__230
D70G	kin	sdm, nat	Dibucaine inhibition	Low inhibition	McGuire_1989_Proc.Natl.Acad.Sci.U.S.A_86_953, Neville_1990_J.Neurosci.Res_27_452, Neville_1992_EMBO.J_11_1641, Ehrlich_1994_Genomics_22_288
D70G	kin	sdm, nat	Aging	D70 and E197 function like check valves for water	Masson_1999_Chem.Biol.Interact_119-120_17
D70G	kin	sdm, nat	Aging	D70G increases half-life of aging by DFP 8 times	Masson_1997_Biochem.J_327_601
D70G	kin	sdm, nat	Aspirin hydrolysis		Masson_1998_Biochim.Biophys.Acta_1387_41
D70N		sdm	Succinylthiocholine binding	Higher Km lower kcat	Masson_1997_Biochemistry_36_2266
D70K		sdm	Succinylthiocholine binding	Higher Km	Masson_1997_Biochemistry_36_2266
D70K		sdm	Aspirin hydrolysis		Masson_1998_Biochim.Biophys.Acta_1387_41
D70Y		sdm	Peripheral Anionic site	interraction 70/332	Masson_1999_Biochim.Biophys.Acta_1433_281
D70G/ Y332A		sdm	Peripheral Anionic site	interraction 70/332	Masson_1999_Biochim.Biophys.Acta_1433_281
D70Y/ Y332D		sdm	Peripheral Anionic site	interraction 70/332	Masson_1999_Biochim.Biophys.Acta_1433_281
D70G/ Y114H		sdm	Dibucaine inhibition, Succinylcholine hydrolysis	Restores function to D70 mutants	Neville_1992_EMBO.J_11_1641
D70G/ S425P		sdm	Succinylcholine hydrolysis/Dibucaine inhibition	S425P exaggerates D70G effects of dibucaine and succinylcholine resistance	Gnatt_1990_Cancer.Res_50_1983, Neville_1990_J.Neurosci.Res_27_452, Neville_1992_EMBO.J_11_1641, Gnatt_1990_Cancer.Res_50_1983, Schwarz_1995_Pharmacol.Th_67_283
D70G/ F561Y		sdm	Succinylcholine hydrolysis	mutation at 561 restores binding of inhibitors on 70 mutant	Neville_1992_EMBO.J_11_1641
D70G/ Y114H/ S425P		sdm	Succinylcholine hydrolysis Dibucaine inhibition	mutations at 561 and 114 restore binding of inhibitors on 70 mutant	Neville_1992_EMBO.J_11_1641, Schwarz_1995_Pharmacol.Ther_67_283
D70G/ Y114H/ F561Y		sdm	Succinylcholine hydrolysis	mutations at 561 and 114 restore binding of inhibitors on 70 mutant	Neville_1992_EMBO.J_11_1641
D70G/ Y114H/ F561Y		sdm	Dibucaine inhibition	mutations at 561 and 114 restore binding of inhibitors on 70 mutant	Neville_1992_EMBO.J_11_1641
D70G/ Y114H/ F561Y		sdm	Natural mutation	Succinylcholine hydrolysis Dibucaine inhibition	Neville_1992_EMBO.J_11_1641
D70G/ E441G/ E443Q		sdm	Succinylcholine hydrolysis	Catalysis reduced activity/Succinylcholine hydrolysis/Dibucaine inhibition 441 and 443 bind succinylcholine but mutant do not bind dibucaine	Neville_1992_EMBO.J_11_1641
D70G/ E441G/ E443Q		sdm	Catalysis	Reduced activity	Neville_1992_EMBO.J_11_1641
D70G/ A539T		nat	Natural mutation	A539T co appears with D70G natural mutation	Bartels_1992_Am.J.Hum.Genet_50_1086

mouse-ACHE : (kinetic parameters)

Mutation	Kin.	Type	Evaluation system	Effect	Reference
Y72N/ D74N/ Y124Q/ W286A	kin	sdm	Peripheral Anionic Site	increase Ki of PAS ligands	Radic_1993_Biochemistry_32_12074
Y72N/ D74N/ Y124Q/ W286R	kin	sdm	Peripheral Anionic Site	increase Ki of PAS ligands	Radic_1993_Biochemistry_32_12074
D74N	kin	sdm	Peripheral Anionic Site	increase Km ACTh slight dim kcat	Radic_1993_Biochemistry_32_12074, Radic_1994_J.Biol.Chem_269_11233
D74N	kin	sdm	Electrostatic	D74N contribute the most to ligand trapping or orientation	Radic_1997_J.Biol.Chem_272_23265
D74N	kin	sdm	Aricept~Donepezil~E2020 inhibition	2300 fold increase Ki vs WT	Saxena_2003_Eur.J.Biochem_270_4447
D74N/ E202Q/ E450Q		sdm	Electrostatic	influence TFK inhibition but not ionic strength dependance	Radic_1997_J.Biol.Chem_272_23265
D74N/ E202Q		sdm	Electrostatic	influence TFK inhibition but not ionic strength dependance	Radic_1997_J.Biol.Chem_272_23265
D74N/ D280V/ D283N		sdm	Electrostatic	mixed active center and surface charge mutant	Radic_1997_J.Biol.Chem_272_23265

torca-ACHE

Mutation	Kin.	Type	Evaluation system	Effect	Reference
D72G		sdm	Substrate inhibition	steric blockade	Mallender_2000_Biochemistry_39_7753

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