F338A_human-ACHE

General

Gene Locus : human-ACHE

Mode of mutation : Site directed mutagenesis

Disease :

Summary : Signal transduction reduced kcat, marginal effect on inhibition by edrophonium 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 Shafferman_1995_5th.ChE.Meeting.Madras__189 Shafferman_1996_Biochem.J_318_833 || Acyl specificity Acyl pocket decreased catalytic activity, orientation of His 447 Barak_2002_Biochemistry_41_8245 Shafferman_2005_Chem.Biol.Interact_157-158_123 || Oxime interaction Cochran_2011_J.Biol.Chem_286_29718

AAA Change :

Allelic Variant :

Risk Factor :

Inhibitor :

Structure :

Disease by interaction :

Interact Gene Locus :

Xenobiotic sensitivity :

Modification : Hydrophobic subsite || Acyl specificity || Signal transduction

Torpedo_number : 331

Kinetic Parameter : Edrophonium_F338A_human-ACHE, Paranitrophenylacetate_F338A_human-ACHE, S-N-Propylthioacetate_F338A_human-ACHE, 3,3-dimethylbutylthioacetate_F338A_human-ACHE, Acetylthiocholine_F338A_human-ACHE, Hexamethonium_F338A_human-ACHE, BW284C51_F338A_human-ACHE, Propidium_F338A_human-ACHE, Decamethonium_F338A_human-ACHE, Tacrine_F338A_human-ACHE, HuperzineA_F338A_human-ACHE

News : No news

Comment :
p.F338A Phe338Ala (p.F369A Phe369Ala in primary sequence with 31 amino-acids signal peptide) Signal transduction: reduced kcat, marginal effect on inhibition by edrophonium\; Acyl pocket decreased catalytic activity, orientation of His 447

References (12)

Title : Oxime-assisted acetylcholinesterase catalytic scavengers of organophosphates that resist aging - Cochran_2011_J.Biol.Chem_286_29718
Author(s) : Cochran R , Kalisiak J , Kucukkilinc TT , Radic Z , Garcia E , Zhang L , Ho KY , Amitai G , Kovarik Z , Fokin VV , Sharpless KB , Taylor P
Ref : Journal of Biological Chemistry , 286 :29718 , 2011
Abstract :
PubMedSearch : Cochran_2011_J.Biol.Chem_286_29718
PubMedID: 21730071

Title : Next generation OP-bioscavengers: a circulatory long-lived 4-PEG hypolysine mutant of F338A-HuAChE with optimal pharmacokinetics and pseudo-catalytic characteristics - Kronman_2010_Chem.Biol.Interact_187_253
Author(s) : Kronman C , Cohen O , Mazor O , Ordentlich A , Raveh L , Velan B , Shafferman A
Ref : Chemico-Biological Interactions , 187 :253 , 2010
Abstract :
PubMedSearch : Kronman_2010_Chem.Biol.Interact_187_253
PubMedID: 20005217

Title : Functional requirements for the optimal catalytic configuration of the AChE active center - Shafferman_2005_Chem.Biol.Interact_157-158_123
Author(s) : Shafferman A , Barak D , Kaplan D , Ordentlich A , Kronman C , Velan B
Ref : Chemico-Biological Interactions , 157-158 :123 , 2005
Abstract :
PubMedSearch : Shafferman_2005_Chem.Biol.Interact_157-158_123
PubMedID: 16256968

Title : The aromatic trapping of the catalytic histidine is essential for efficient catalysis in acetylcholinesterase - Barak_2002_Biochemistry_41_8245
Author(s) : Barak D , Kaplan D , Ordentlich A , Ariel N , Velan B , Shafferman A
Ref : Biochemistry , 41 :8245 , 2002
Abstract :
PubMedSearch : Barak_2002_Biochemistry_41_8245
PubMedID: 12081473

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 :
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 :
PubMedSearch : Shafferman_1996_Biochem.J_318_833
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
Abstract :
PubMedSearch : Barak_1994_J.Biol.Chem_269_6296
PubMedID: 8119978

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 :
PubMedSearch : Ordentlich_1993_J.Biol.Chem_268_17083
PubMedID: 8349597
Gene_locus related to this paper: human-ACHE , human-BCHE

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
Abstract :
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: