D74N_human-ACHE

General

Gene Locus : human-ACHE

Mode of mutation : Site directed mutagenesis

Disease :

Summary : Omega loop No effect Velan_1996_FEBS.Lett_395_22 || 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 || 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 || Heat and pressure stability strengthened heat or pressure stability Clery-Barraud_2002_Eur.J.Biochem_269_4297 || VX stereospecificity decrease in stereoselectivity Ordentlich_2004_Biochemistry_43_11255 Ordentlich_2005_Chem.Biol.Interact_157-158_191 || 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

AAA Change :

Allelic Variant :

Risk Factor :

Inhibitor :

Structure :

Disease by interaction :

Interact Gene Locus :

Xenobiotic sensitivity :

Modification : Omega loop || Peripheral Anionic Site || Substrate inhibition || Heat and pressure stability || Stability || Oxime interaction

Torpedo_number : 72

Kinetic Parameter : Acetylthiocholine_D74N_human-ACHE, Edrophonium_D74N_human-ACHE, Hexamethonium_D74N_human-ACHE, BW284C51_D74N_human-ACHE, Propidium_D74N_human-ACHE, Decamethonium_D74N_human-ACHE, Tacrine_D74N_human-ACHE, HuperzineA_D74N_human-ACHE

News : No news

Comment :
p.D74N Asp74Asn (p.D105N Asp105Asn in primary sequence with 31 amino-acids signal peptide) Substrate inhibition\;Signal transduction Affects conformation of active site and PAS\; strengthened heat or pressure stability \;decrease in VX stereoselectivity\; 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

References (12)

Title : Reactivation of tabun-hAChE investigated by structurally analogous oximes and mutagenesis - Artursson_2009_Toxicology_265_108
Author(s) : Artursson E , Akfur C , Hornberg A , Worek F , Ekstrom F
Ref : Toxicology , 265 :108 , 2009
PubMedID: 19761810

Title : The role of AChE active site gorge in determining stereoselectivity of charged and noncharged VX enantiomers - Ordentlich_2005_Chem.Biol.Interact_157-158_191
Author(s) : Ordentlich A , Barak D , Sod-Moriah G , Kaplan D , Mizrahi D , Segall Y , Kronman C , Karton Y , Lazar A , Marcus D , Velan B , Shafferman A
Ref : Chemico-Biological Interactions , 157-158 :191 , 2005
PubMedID: 16289014

Title : Stereoselectivity toward VX is determined by interactions with residues of the acyl pocket as well as of the peripheral anionic site of AChE - Ordentlich_2004_Biochemistry_43_11255
Author(s) : Ordentlich A , Barak D , Sod-Moriah G , Kaplan D , Mizrahi D , Segall Y , Kronman C , Karton Y , Lazar A , Marcus D , Velan B , Shafferman A
Ref : Biochemistry , 43 :11255 , 2004
PubMedID: 15366935

Title : Pressure and heat inactivation of recombinant human acetylcholinesterase. Importance of residue E202 for enzyme stability - Clery-Barraud_2002_Eur.J.Biochem_269_4297
Author(s) : Clery-Barraud C , Ordentlich A , Grosfeld H , Shafferman A , Masson P
Ref : European Journal of Biochemistry , 269 :4297 , 2002
PubMedID: 12199708

Title : The 'aromatic patch' of three proximal residues in the human acetylcholinesterase active centre allows for versatile interaction modes with inhibitors - Ariel_1998_Biochem.J_335_95
Author(s) : Ariel N , Ordentlich A , Barak D , Bino T , Velan B , Shafferman A
Ref : Biochemical Journal , 335 :95 , 1998
PubMedID: 9742217

Title : Structural modifications of the omega loop in human acetylcholinesterase - Velan_1996_FEBS.Lett_395_22
Author(s) : Velan B , Barak D , Ariel N , Leitner M , Bino T , Ordentlich A , Shafferman A
Ref : FEBS Letters , 395 :22 , 1996
PubMedID: 8849682

Title : Aging of phosphylated human acetylcholinesterase: catalytic processes mediated by aromatic and polar residues of the active centre - Shafferman_1996_Biochem.J_318_833
Author(s) : Shafferman A , Ordentlich A , Barak D , Stein D , Ariel N , Velan B
Ref : Biochemical Journal , 318 :833 , 1996
PubMedID: 8836126

Title : Molecular Aspects of Catalysis and of Allosteric Regulation of Aceytlcholinesterases -
Author(s) : Shafferman A , Ordentlich A , Barak D , Kronman C , Ariel N , Leitner M , Segall Y , Bromberg A , Reuveny S , Marcus D , Bino T , Lazar A , Cohen S , Velan B
Ref : In Enzyme of the Cholinesterase Family - Proceedings of Fifth International Meeting on Cholinesterases , (Quinn, D.M., Balasubramanian, A.S., Doctor, B.P., Taylor, P., Eds) Plenum Publishing Corp. :189 , 1995
PubMedID:

Title : Acetylcholinesterase peripheral anionic site degeneracy conferred by amino acid arrays sharing a common core - Barak_1994_J.Biol.Chem_269_6296
Author(s) : Barak D , Kronman C , Ordentlich A , Ariel N , Bromberg A , Marcus D , Lazar A , Velan B , Shafferman A
Ref : Journal of Biological Chemistry , 269 :6296 , 1994
PubMedID: 8119978

Title : Recombinant human acetylcholinesterase - Enzyme engineering -
Author(s) : Shafferman A , Velan B , Barak D , Kronman C , Ordentlich A , Flashner Y , Leitner M , Segal Y , Grosfeld H , Stein D , Ariel N
Ref : Medical Defense Bioscience Review , 3 :1097 , 1993
PubMedID:

Title : Substrate inhibition of acetylcholinesterase: residues affecting signal transduction from the surface to the catalytic center - Shafferman_1992_EMBO.J_11_3561
Author(s) : Shafferman A , Velan B , Ordentlich A , Kronman C , Grosfeld H , Leitner M , Flashner Y , Cohen S , Barak D , Ariel N
Ref : EMBO Journal , 11 :3561 , 1992
PubMedID: 1396557

Title : Acetylcholinesterase Catalysis - Protein Engineering Studies -
Author(s) : Shafferman A , Velan B
Ref : In Multidisciplinary approaches to cholinesterase functions - Proceedings of Fourth International Meeting on Cholinesterases , (Shafferman, A. and Velan, B., Eds) Plenum Press, New York :165 , 1992
PubMedID: