E202D_human-ACHE

General

Gene Locus : human-ACHE

Mode of mutation : Site directed mutagenesis

Disease :

Summary : Catalysis Decrease in catalytic and bimolecular constant, identical effect on charge and uncharged substrate, affects acylation-deacylation steps and not the noncovalent complex formation 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 E202 mutant not inhibited at high substrate concentration 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 || Acylation,Phosphorylation low effect on inhibition by DFP and DEFP but high for Paraoxon Ordentlich_1995_5th.ChE.Meeting.Madras__221 Ordentlich_1996_J.Biol.Chem_271_11953 Shafferman_1996_Biochem.J_318_833 || Aging E202 contributes to the aging process by stabilizing the imidazolium His447 Shafferman_1996_Biochem.J_318_833

AAA Change :

Allelic Variant :

Risk Factor :

Inhibitor :

Structure :

Disease by interaction :

Interact Gene Locus :

Xenobiotic sensitivity :

Modification : Acylation,Phosphorylation || Substrate inhibition || Aging

Torpedo_number : 199

Kinetic Parameter : BW284C51_E202D_human-ACHE, Decamethonium_E202D_human-ACHE, Propidium_E202D_human-ACHE, Edrophonium_E202D_human-ACHE, Acetylthiocholine_E202D_human-ACHE

News : No news

Comment : p.E202D Glu202Asp (p.E233D Glu233Asp in primary sequence with 31 amino-acids signal peptide) Catalysis\;Decrease in catalytic and bimolecular constant, identical effect on charge and uncharged substrate, affects acylation-deacylation steps and not the noncovalent complex formation\; not inhibited at high substrate concentration\; Acylation,Phosphorylation: low effect on inhibition by DFp and DEFP but high for Paraoxon\; Aging:E202 contributes to the aging process by stabilizing the imidazolium His447

References (8)

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
Abstract : Ordentlich_1996_J.Biol.Chem_271_11953
ESTHER : Ordentlich_1996_J.Biol.Chem_271_11953
PubMedSearch : Ordentlich_1996_J.Biol.Chem_271_11953
PubMedID: 8662593

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 : 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 : 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 : 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: