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| Content Provider | PubMed Central |
|---|---|
| Author | Pattison, S. Bernhard, S. |
| Abstract | The effect of a class of ligands on the catalytic activity of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) from Torpedo californica electroplax tissue has been studied via the transient reaction of a fluorophoric acetylcholine analog, 7-(N,N-dimethyl)carbamoxy-N-methylquinolinium iodide (M7C). These "peripheral" ligands inhibit the formation of a metastable carbamyl-enzyme intermediate from M7C. They induce slow isomerization to a new conformational state that shows little or no reaction with M7C. At saturating ligand concentration, the unimolecular isomerization rate constant is 0.03 +/- 0.01 sec-1, a slow rate compared to the rate of carbamylation of the active conformation. Peripheral ligands alter the distribution between reactive and unreactive conformations, thus inducing biphasic rates and amplitudes of carbamylation. The amplitudes, but not the two specific rates, are affected by the concentration of ligand. Zn2+ and d-tubocurarine are two ligands that induce the same slow isomerization rate. On the basis of this identity of function by ligands of disparate structure, we postulate the existence of only a single active conformation and a single inactive conformation (stabilized by interaction with both ligands). In the absence of ligands, the active conformation predominates. Peripheral ligands bind specifically to the inactive conformation. Alkaline earth cations such as Ca2+ and Mg2+ interact strongly and preferentially with the active conformation and drive the conformational equilibrium toward the active state. Ligand-induced inactivation is observed both with highly purified trypsin-solubilized enzyme and with enzyme bound to unfractionated membrane fragments. |
| Starting Page | 3613 |
| File Format | |
| ISSN | 10916490 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 8 |
| Volume Number | 75 |
| Language | English |
| Publisher Date | 1978-08-01 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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