F295A_human-ACHE

General

Gene Locus : human-ACHE

Mode of mutation : Site directed mutagenesis

Disease :

Summary : 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 || 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 || Acyl specificity Acyl pocket, decreased catalytic activity, orientation of His 447 Barak_2002_Biochemistry_41_8245 || VX stereospecificity decrease in stereoselectivity Ordentlich_2004_Biochemistry_43_11255 Ordentlich_2005_Chem.Biol.Interact_157-158_191

AAA Change :

Allelic Variant :

Risk Factor :

Inhibitor :

Structure :

Disease by interaction :

Interact Gene Locus :

Xenobiotic sensitivity :

Modification : Acyl specificity

Torpedo_number : 288

Kinetic Parameter : Acetylthiocholine_F295A_human-ACHE, Edrophonium_F295A_human-ACHE, Hexamethonium_F295A_human-ACHE, BW284C51_F295A_human-ACHE, Propidium_F295A_human-ACHE, Decamethonium_F295A_human-ACHE, Tacrine_F295A_human-ACHE, HuperzineA_F295A_human-ACHE

News : No news

Comment :
p.F295A Phe295Ala (p.F326A Phe326Ala in primary sequence with 31 amino-acids signal peptide) Acyl specificity\;Acyl pocket, OP-specificity.inhanced affinity for BTC\; increased reactivity to DFP DEFP and paraoxon, decreased catalytic activity, orientation of His 447

References (11)

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 : 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
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
PubMedID: 9742217

Title : The architecture of human acetylcholinesterase active center probed by interactions with selected organophosphate inhibitors - Ordentlich_1996_J.Biol.Chem_271_11953
Author(s) : Ordentlich A , Barak D , Kronman C , Ariel N , Segall Y , Velan B , Shafferman A
Ref : Journal of Biological Chemistry , 271 :11953 , 1996
PubMedID: 8662593

Title : Amino Acids Determining Specificity to OP-Agents and Facilitating the Aging Process in Human Acetylcholinesterase -
Author(s) : Ordentlich A , Kronman C , Stein D , Ariel N , Reuveny S , Marcus D , Segall Y , Barak D , Velan B , Shafferman A
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. :221 , 1995
PubMedID:

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 : Role of tyrosine 337 in the binding of huperzine A to the active site of human acetylcholinesterase - Ashani_1994_Mol.Pharmacol_45_555
Author(s) : Ashani Y , Grunwald J , Kronman C , Velan B , Shafferman A
Ref : Molecular Pharmacology , 45 :555 , 1994
PubMedID: 8145739
Gene_locus related to this paper: human-ACHE

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
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: