Currier S F, Mautner H G
Biochemistry. 1977 May 3;16(9):1944-8. doi: 10.1021/bi00628a029.
The finding that methyl methanethiolsulfonate appears to inhibit choline acetyltransferase from squid ganglia not by reacting with a thiol group of the enzyme but by reacting with the thiol group of coenzyme A to form a competitive inhibitor of acetyl coenzyme A led to the synthesis of the ethyl, propyl, and 3-carboxy-4-nitrophenyl disulfides of CoA. The methyl disulfide of 1,N6-etheno-C0A, a fluorescent ligand, was also prepared. All the disulfides are powerful inhibitors of ChA, their Ki values being very similar. The Km values for acetylpropionyl-, and butyryl-CoA were also found to be similar; however, modification of the acyl group alter the Km values for choline. CoA, and dethia-CoA, showed similar abilities to be bound to ChA; however, the 3'-phospho groups of acetyl CoA and CoA appear to be of importance in interacting with the enzyme. 8-Anilino-1-naphthalenesulfonate is a competitive inhibitor of acetyl-CoA binding.
甲硫醇磺酸甲酯似乎不是通过与鱿鱼神经节胆碱乙酰转移酶的硫醇基团反应，而是通过与辅酶A的硫醇基团反应形成乙酰辅酶A的竞争性抑制剂来抑制该酶，这一发现促使人们合成了辅酶A的乙基、丙基和3-羧基-4-硝基苯基二硫化物。还制备了1,N6-乙烯基辅酶A的甲基二硫化物，一种荧光配体。所有二硫化物都是胆碱乙酰转移酶的强效抑制剂，它们的抑制常数（Ki）值非常相似。还发现乙酰丙酰辅酶A和丁酰辅酶A的米氏常数（Km）值相似；然而，酰基的修饰会改变胆碱的Km值。辅酶A和去硫辅酶A显示出与胆碱乙酰转移酶结合的相似能力；然而，乙酰辅酶A和辅酶A的3'-磷酸基团在与该酶相互作用中似乎很重要。8-苯胺基-1-萘磺酸盐是乙酰辅酶A结合的竞争性抑制剂。
