Three point mutations of human butyrylcholinesterase in a Japanese family and the alterations of three-dimensional structure.
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Asanuma K, Yagihashi A, Uehara N, Kida T, Watanabe N
Three point mutations of human butyrylcholinesterase in a Japanese family and the alterations of three-dimensional structure.
Clin Chim Acta. 1999 May;283(1-2):33-42.
- PubMed ID
- 10404729 [ View in PubMed]
- Abstract
Three different mutations at codons 330 (TTA to ATA), 365 (GGA to AGA) and 515 (CGT to TGT) of human butyrylcholinesterase (hBChE) were identified in a Japanese family. We correlated alterations in in the patient's hBChE activity with possible structural alterations in the three-dimensional structure of hBChE caused by the point mutations. This study was performed using the published computer-generated three-dimensional structure of hBChE based on the structure of acetylcholinesterase. The amino acid substitution at L330I was adjacent to hydrophobic residues that form the channel domain of the active center. This side chain faced the side opposite the active center. The amino acid substitution at G365R was located at the position most remote from the active center, and this substitution site was exposed to the surface of the BChE protein. Alpha-helical structure was present to the active center, and the guanidyl residue of native Arg 515 was hydrogen-bonded to the carboxyl group of Asp 395 in the alpha-helix. These point mutations may cause steric effects on the present patient's hBChE activity. This is the first report of three-dimensional structural analysis performed on the L330I, G365R, and R515C mutations of hBChE.