Interaction of analogs of coenzyme A with choline acetyltransferase

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Abstract
The finding that methyl methanethiosulfonate appears to inhibit choline acetyltransferase (EC 2.3.1.6) 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-CoA, a fluorescent ligand, was also prepared. All the disulfides are powerful inhibitors of ChA, their Ki values being very similar. The Km values for acetyl-, propionyl-, and butyryl-CoA were also found to be similar; however, modification of the acyl group alters 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.