Gene Locus : human-ACHE
Mode of mutation : Site directed mutagenesis
Disease :
Summary : Signal transduction Decrease in catalytic and apparent bimolecular constant Shafferman_1992_EMBO.J_11_3561 Barak_1994_J.Biol.Chem_269_6296 Ordentlich_1995_J.Biol.Chem_270_2082 || Substrate inhibition absence of substrate inhibition Shafferman_1992_EMBO.J_11_3561 Barak_1994_J.Biol.Chem_269_6296 Ordentlich_1995_J.Biol.Chem_270_2082 || Oxime interaction Cochran_2011_J.Biol.Chem_286_29718 || Acyl specificity replacement of aromatic active center residues in human-ACHE by the corresponding residues in human-BCHE Kaplan_2001_Biochemistry_40_7433 || oxime interaction reactivation of tabun-inhibited human AChE. 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 : Signal transduction || Substrate inhibition || Oxime interaction || Acyl specificity
Torpedo_number : 330
Kinetic Parameter : Edrophonium_Y337A_human-ACHE, Paranitrophenylacetate_Y337A_human-ACHE, S-N-Propylthioacetate_Y337A_human-ACHE, 3,3-dimethylbutylthioacetate_Y337A_human-ACHE, Acetylthiocholine_Y337A_human-ACHE, Hexamethonium_Y337A_human-ACHE, BW284C51_Y337A_human-ACHE, Propidium_Y337A_human-ACHE, Decamethonium_Y337A_human-ACHE, Tacrine_Y337A_human-ACHE, HuperzineA_Y337A_human-ACHE, Butyrylthiocholine_Y337A_human-ACHE
News : No news
Comment :
p.Y337A Tyr337Ala (p.Y368A Tyr368Ala in primary sequence with 31 amino-acids signal peptide)\;Decrease in catalytic and apparent bimolecular constant Substrate inhibition\;absence of substrate inhibition\; Acyl specificity\;replacement of aromatic active center residues in human-ACHE by the corresponding residues in human-BCHE\; Oxime interaction\; reactivation of tabun-inhibited human AChE. Unable to facilitate HI-6-mediated reactivation of tabun-hAChE\; The phosphoramidated-hAChE choline-binding site mutant Y337A showed three-times enhanced reactivation capacity with non-triazole imidazole containing aldoximes than with 2PAM
| Title : Counteracting tabun inhibition by reactivation by pyridinium aldoximes that interact with active center gorge mutants of acetylcholinesterase - Kovarik_2019_Toxicol.Appl.Pharmacol_372_40 |
| Author(s) : Kovarik Z , Macek Hrvat N , Kalisiak J , Katalinic M , Sit RK , Zorbaz T , Radic Z , Fokin VV , Sharpless KB , Taylor P |
| Ref : Toxicol Appl Pharmacol , 372 :40 , 2019 |
| Abstract : |
| PubMedSearch : Kovarik_2019_Toxicol.Appl.Pharmacol_372_40 |
| PubMedID: 30978400 |
| Gene_locus related to this paper: human-ACHE |
| Title : HI-6 assisted catalytic scavenging of VX by acetylcholinesterase choline binding site mutants - Macek Hrvat_2016_Chem.Biol.Interact_259_148 |
| Author(s) : Macek Hrvat N , Zunec S , Taylor P , Radic Z , Kovarik Z |
| Ref : Chemico-Biological Interactions , 259 :148 , 2016 |
| Abstract : |
| PubMedSearch : Macek Hrvat_2016_Chem.Biol.Interact_259_148 |
| PubMedID: 27083141 |
| Gene_locus related to this paper: human-ACHE |
| Title : Centrally acting oximes in reactivation of tabun-phosphoramidated AChE - Kovarik_2013_Chem.Biol.Interact_203_77 |
| Author(s) : Kovarik Z , Macek Hrvat N , Sit RK , Radic Z , Fokin VV , Sharpless KB , Taylor P |
| Ref : Chemico-Biological Interactions , 203 :77 , 2013 |
| Abstract : |
| PubMedSearch : Kovarik_2013_Chem.Biol.Interact_203_77 |
| PubMedID: 22960624 |
| Title : Oxime-assisted acetylcholinesterase catalytic scavengers of organophosphates that resist aging - Cochran_2011_J.Biol.Chem_286_29718 |
| Author(s) : Cochran R , Kalisiak J , Tuylu Kucukkilinc T , 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 : 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 |
| Abstract : |
| PubMedSearch : Artursson_2009_Toxicology_265_108 |
| PubMedID: 19761810 |
| Title : Does butyrylization of acetylcholinesterase through substitution of the six divergent aromatic amino acids in the active center gorge generate an enzyme mimic of butyrylcholinesterase? - Kaplan_2001_Biochemistry_40_7433 |
| Author(s) : Kaplan D , Ordentlich A , Barak D , Ariel N , Kronman C , Velan B , Shafferman A |
| Ref : Biochemistry , 40 :7433 , 2001 |
| Abstract : |
| PubMedSearch : Kaplan_2001_Biochemistry_40_7433 |
| PubMedID: 11412096 |
| 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 : 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 : |
| PubMedSearch : Ordentlich_1995_J.Biol.Chem_270_2082 |
| PubMedID: 7836436 |
| 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 : 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 |