W86A_human-ACHE

General

Gene Locus : human-ACHE

Mode of mutation : Site directed mutagenesis

Disease :

Summary : Choline binding site Choline binding site\/signal transductioncation-aromatic interaction, 660 fold decrease affinity for ACTh no effect on uncharged substrate, Shafferman_1992_EMBO.J_11_3561 Shafferman_1992_4th.ChE.Meeting.Eilat__165 Ordentlich_1993_J.Biol.Chem_268_17083 Shafferman_1993_Proc.Med.Def.Biosci.Rev_3_1097 Barak_1994_J.Biol.Chem_269_6296 Kronman_1994_J.Biol.Chem_269_27819 || Signal transduction Y133 maintains the correct orientation of W86 Shafferman_1995_5th.ChE.Meeting.Madras__189 Ordentlich_1995_J.Biol.Chem_270_2082 Shafferman_1996_Biochem.J_318_833

AAA Change :

Allelic Variant :

Risk Factor :

Inhibitor :

Structure :

Disease by interaction :

Interact Gene Locus :

Xenobiotic sensitivity :

Modification : Choline binding site || Signal transduction

Torpedo_number : 84

Kinetic Parameter : Edrophonium_W86A_human-ACHE, Paranitrophenylacetate_W86A_human-ACHE, S-N-Propylthioacetate_W86A_human-ACHE, 3,3-dimethylbutylthioacetate_W86A_human-ACHE, Acetylthiocholine_W86A_human-ACHE, Hexamethonium_W86A_human-ACHE, BW284C51_W86A_human-ACHE, Propidium_W86A_human-ACHE, Decamethonium_W86A_human-ACHE, Tacrine_W86A_human-ACHE, HuperzineA_W86A_human-ACHE

News : No news

Comment : p.W86A Trp86Ala (p.W117A Trp117Ala in primary sequence with 31 amino-acids signal peptide) Choline binding site\/signal transductioncation-aromatic interaction, 660 fold decrease affinity for ACTh no effect on uncharged substrate, Y133 maintains the correct orientation of W86

References (10)

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
Abstract : Ariel_1998_Biochem.J_335_95
ESTHER : Ariel_1998_Biochem.J_335_95
PubMedSearch : Ariel_1998_Biochem.J_335_95
PubMedID: 9742217

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
Abstract : Shafferman_1996_Biochem.J_318_833
ESTHER : Shafferman_1996_Biochem.J_318_833
PubMedSearch : Shafferman_1996_Biochem.J_318_833
PubMedID: 8836126

Title : Contribution of aromatic moieties of tyrosine 133 and of the anionic subsite tryptophan 86 to catalytic efficiency and allosteric modulation of acetylcholinesterase - Ordentlich_1995_J.Biol.Chem_270_2082
Author(s) : Ordentlich A , Barak D , Kronman C , Ariel N , Segall Y , Velan B , Shafferman A
Ref : Journal of Biological Chemistry , 270 :2082 , 1995
Abstract : Ordentlich_1995_J.Biol.Chem_270_2082
ESTHER : Ordentlich_1995_J.Biol.Chem_270_2082
PubMedSearch : Ordentlich_1995_J.Biol.Chem_270_2082
PubMedID: 7836436

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
Abstract : Barak_1994_J.Biol.Chem_269_6296
ESTHER : Barak_1994_J.Biol.Chem_269_6296
PubMedSearch : Barak_1994_J.Biol.Chem_269_6296
PubMedID: 8119978

Title : The back door hypothesis for product clearance in acetylcholinesterase challenged by site-directed mutagenesis - Kronman_1994_J.Biol.Chem_269_27819
Author(s) : Kronman C , Ordentlich A , Barak D , Velan B , Shafferman A
Ref : Journal of Biological Chemistry , 269 :27819 , 1994
Abstract : Kronman_1994_J.Biol.Chem_269_27819
ESTHER : Kronman_1994_J.Biol.Chem_269_27819
PubMedSearch : Kronman_1994_J.Biol.Chem_269_27819
PubMedID: 7961709

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 : Dissection of the human acetylcholinesterase active center determinants of substrate specificity. Identification of residues constituting the anionic site, the hydrophobic site, and the acyl pocket - Ordentlich_1993_J.Biol.Chem_268_17083
Author(s) : Ordentlich A , Barak D , Kronman C , Flashner Y , Leitner M , Segall Y , Ariel N , Cohen S , Velan B , Shafferman A
Ref : Journal of Biological Chemistry , 268 :17083 , 1993
Abstract : Ordentlich_1993_J.Biol.Chem_268_17083
ESTHER : Ordentlich_1993_J.Biol.Chem_268_17083
PubMedSearch : Ordentlich_1993_J.Biol.Chem_268_17083
PubMedID: 8349597
Gene_locus related to this paper: human-ACHE , human-BCHE

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
Abstract : Shafferman_1992_EMBO.J_11_3561
ESTHER : Shafferman_1992_EMBO.J_11_3561
PubMedSearch : Shafferman_1992_EMBO.J_11_3561
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: