D70G_human-BCHE

Gene Locus : human-BCHE

Mode of mutation : Site directed mutagenesis || Natural mutant

Disease :

Summary : Succinylthiocholine binding Higher Km for charged substrates Masson_1997_Biochemistry_36_2266 || Peripheral Anionic Site Higher Km for substrates Loewenstein-Lichtenstein_1996_Mol.Pharmacol_50_1423 || Succinylcholine hydrolysis Low hydrolysis McGuire_1989_Proc.Natl.Acad.Sci.U.S.A_86_953 Neville_1990_J.Neurosci.Res_27_452 Neville_1992_EMBO.J_11_1641 Ehrlich_1994_Genomics_22_288 Masson_1995_5th.ChE.Meeting.Madras__230 || Atypical variant Low hydrolysis McGuire_1989_Proc.Natl.Acad.Sci.U.S.A_86_953 Neville_1990_J.Neurosci.Res_27_452 Neville_1992_EMBO.J_11_1641 Ehrlich_1994_Genomics_22_288 Masson_1995_5th.ChE.Meeting.Madras__230 || Dibucaine inhibition Low inhibition McGuire_1989_Proc.Natl.Acad.Sci.U.S.A_86_953 Neville_1990_J.Neurosci.Res_27_452 Neville_1992_EMBO.J_11_1641 Ehrlich_1994_Genomics_22_288 || Aging D70 and E197 function like check valves for water Masson_1999_Chem.Biol.Interact_119-120_17 || Aging D70G increases half-life of aging by DFP 8 times Masson_1997_Biochem.J_327_601 || Aspirin hydrolysis Masson_1998_Biochim.Biophys.Acta_1387_41

AAA Change :

Allelic Variant :

Risk Factor :

Inhibitor :

Structure :

Disease by interaction :

Interact Gene Locus :

Xenobiotic sensitivity : Defect in Suxamethonium hydrolysis

Modification : Peripheral Anionic Site || Succinylthiocholine binding || Aging || Atypical variant

Torpedo_number : 72

Kinetic Parameter : Acetylcholine_D70G_human-BCHE, Propionylcholine_D70G_human-BCHE, Butyrylcholine_D70G_human-BCHE, Pentanoylcholine_D70G_human-BCHE, Hexanoylcholine_D70G_human-BCHE, Heptanoylcholine_D70G_human-BCHE, Benzoylcholine_D70G_human-BCHE, Succinyldithiocholine_D70G_human-BCHE, Heroin_D70G_human-BCHE, Procaine_D70G_human-BCHE, Tetracaine_D70G_human-BCHE, O-Nitrophenylbutyrate_D70G_human-BCHE, 1-Naphtylacetate_D70G_human-BCHE, Methylprednisolone-acetate_D70G_human-BCHE, Aspirin_D70G_human-BCHE, Choline_D70G_human-BCHE, Tetramethylammonium_D70G_human-BCHE, Meperidine_D70G_human-BCHE, Succinylcholine~Suxamethonium_D70G_human-BCHE, Decamethonium_D70G_human-BCHE, Chlorpromazine_D70G_human-BCHE, Dibucaine_D70G_human-BCHE, Win5303_D70G_human-BCHE, Win4510_human-BCHE, Vecuronium_D70G_human-BCHE, Pancuronium_D70G_human-BCHE, 17-desoxypancuronium_D70G_human-BCHE, Neostigmine~Prostigmine_D70G_human-BCHE, Dibutyrate-pancuronium_D70G_human-BCHE, Physostigmine~Eserine_D70G_human-BCHE, Ro-2-0683_D70G_human-BCHE, Butyrylthiocholine_D70G_human-BCHE, Tacrine_D70G_human-BCHE, Solanine_D70G_human-BCHE, BW284C51_D70G_human-BCHE, Cocaine_D70G_human-BCHE

News : No news

Comment : p.D70G Asp70Gly c.293A>G (p.D98G Asp98Gly in primary sequence with 28 amino-acids signal peptide) rs1799807, Atypical variant, CHE1*A, Dibucaine-resistant I CHE*70G, the classic deficiency variant described by Kalow and Gunn (1959), Kalow and Staron (1957) , has a homozygote frequency of about 1:3,000 in white North Americans. (from OMIM) McGuire et al. (1989) found that a mutation in nucleotide 209, which changes codon 70 from GAT to GGT, was the abnormality in all 5 atypical cholinesterase families examined. The mutation caused the loss of a Sau3A1 restriction site. The gene change results in a substitution of glycine for aspartic acid as amino acid 70. This is an acidic to neutral amino acid change which accounts for the reduced affinity of atypical cholinesterase for choline esters. Aspartic acid must be an important component of the anionic site. Atypical BCHE, the classic deficiency variant described by Kalow (1962), Kalow and Gunn (1959), Kalow and Staron (1957), has a homozygote frequency of about 1:3,000 in white North Americans. In the nomenclature system of La Du et al. (1991), this allelic variant is referred to as CHE*70G. Reduced enzyme activity with butyrylthiocholine as substrate\; \; 2-fold lower affinity for butyrylthiocholine\; 10-fold lower affinity for butyrylthiocholine at homozygosity rs1799807