AN ELECTROSTATIC MECHANISM FOR SUBSTRATE GUIDANCE DOWN THE AROMATIC GORGE OF ACETYLCHOLINESTERASE
AN ELECTROSTATIC MECHANISM FOR SUBSTRATE GUIDANCE DOWN THE AROMATIC GORGE OF ACETYLCHOLINESTERASE
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DOI：
10.1073/pnas.90.11.5128
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发表时间：
1993-06-01
影响因子：
11.1
通讯作者：
SUSSMAN, JL
中科院分区：
文献类型：
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作者：
RIPOLL, DR;FAERMAN, CH;SUSSMAN, JL
静电计算的基础上最近解决的乙酰胆碱酯酶（乙酰胆碱乙酰水解酶，EC 3.1.1.7）的晶体结构表明，这种酶具有很强的静电偶极子。偶极子与通向其活性位点的峡谷对齐，使得带正电的底物将被其静电场吸引到活性位点。在峡谷内，芳香族侧链似乎屏蔽了底物与大多数带负电荷的残基的直接相互作用，这些残基产生偶极子。季铵化合物对芳香环的亲和力，加上这种静电力，可能会协同工作，以创建一个选择性和有效的底物结合位点的乙酰胆碱酯酶，并解释为什么活性位点位于深峡谷的底部内衬与芳香残基。
Electrostatic calculations based on the recently solved crystal structure of acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7) indicate that this enzyme has a strong electrostatic dipole. The dipole is aligned with the gorge leading to its active site, so that a positively charged substrate will be drawn to the active site by its electrostatic field. Within the gorge, aromatic side chains appear to shield the substrate from direct interaction with most of the negatively charged residues that give rise to the dipole. The affinity of quaternary ammonium compounds for aromatic rings, coupled with this electrostatic force, may work in concert to create a selective and efficient substrate-binding site in acetylcholinesterase and explain why the active site is situated at the bottom of a deep gorge lined with aromatic residues.