Asanuma K, Yagihashi A, Uehara N, Kida T, Watanabe N
Department of Laboratory Diagnosis, Sapporo Medical University School of Medicine, Japan.
Clin Chim Acta. 1999 May;283(1-2):33-42. doi: 10.1016/s0009-8981(99)00030-3.
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.
在一个日本家族中发现了人类丁酰胆碱酯酶（hBChE）密码子330（TTA突变为ATA）、365（GGA突变为AGA）和515（CGT突变为TGT）处的三种不同突变。我们将患者hBChE活性的改变与由点突变引起的hBChE三维结构中可能的结构改变相关联。本研究使用基于乙酰胆碱酯酶结构已发表的hBChE计算机生成三维结构进行。L330I处的氨基酸取代与形成活性中心通道结构域的疏水残基相邻。该侧链面向活性中心的对侧。G365R处的氨基酸取代位于距离活性中心最远的位置，且该取代位点暴露于BChE蛋白表面。活性中心存在α-螺旋结构，天然精氨酸515的胍基残基与α-螺旋中天冬氨酸395的羧基形成氢键。这些点突变可能对该患者的hBChE活性产生空间效应。这是对hBChE的L330I、G365R和R515C突变进行三维结构分析的首次报告。
