Conformational analysis of d-tubocurarine: Implications for minimal dimensions of its binding site within ion channels
Tóm tắt
All the minimum-energy conformations of d-tubocurarine were calculated by the method of molecular mechanics. The energy was minimized from 413 closed forms of the 18-member ring. The set of minimum-energy conformations includes 10 forms with energies less than 6 kcal/mol from the most stable one. Among the four lowest minimum-energy conformations, two forms correspond to those known from X-ray studies, whereas two conformations were not detected experimentally earlier. The flexibility of d-tubocurarine was estimated by calculating six paths of interconversion between the four lowest minimum-energy conformations. Using a molecular graphics technique, it was found that the most extended minimum-energy conformation of d-tubocurarine may fit in an ion channel of a rectangular profile of 8.7 × 11.2 Å, while one tetrahydroisoquinoline head may fit a profile as small as 6.9 × 11.0 Å. A possible model of d-tubocurarine location within the ion channel of the neuronal nicotinic acetylcholine receptor is suggested.
Tài liệu tham khảo
Ascher, P., Large, W.A., Rang, H.P. 1979. Studies on the mechanism of action of acetylcholine antagonists on rat parasympathetic ganglion cells. J. Physiol. 295:139–170
Charnet, P., Labarca, C., Leonard, R., Vogelaar, N., Czyzyk, L., Gouin, A., Davidson, N., Lester, H.A. 1990. An openchannel blocker interacts with adjacent turns of α-helices in the nicotinic acetylcholine receptor. Neuron 4:87–95
Codding, P.W., James, M.N.G. 1973. The crystal and molecular structure of a potent neuromuscular blocking agent: d-tubocurarine dichloride pentahydrate. Acta Crystallogr. B29:935–942
Colquhoun, D., Dreyer, F., Sheridan, R. 1979. The actions of tubocurarine at the frog neuromuscular junction. J. Physiol. 293:247–284
Dashevskiy, V.G. 1974. Conformations of Organic Molecules, pp. 1–432. Khimiya, Moscow (in Russian)
Furois-Corbin, S., Pullman, A. 1989a. A possible model for the inner wall of the acetylcholine receptor channel. Biochim. Biophys. Acta 984:339–351
Furois-Corbin, S., Pullman, A. 1989b. Energy profiles in the acetylcholine receptor (AChR) channel. The Mil-helix model and the role of the remaining helices. FEBS Lett. 252:63–68
Go, N., Scheraga, H.A. 1970. Ring closure and local conformational deformations of chain molecules. Macromolecules 3:178–187
Katz, B., Miledi, R. 1978. A re-examination of curare action at the motor end-plate. Proc. Roy. Soc. London B. 203:119–133
Manalis, R.S. 1977. Voltage-dependent effect of curare at the frog neuromuscular junction. Nature 267:366–367
Maslov, V.G. 1977. A program for CNDO/2 calculation of compounds containing up to 232 orbitals. Zh. Strukt. Khimii 18:414–415 (in Russian)
Michelson, M.J., Zeimal, E.V. 1973. Acetylcholine. An Approach to the Molecular Mechanism of Action, pp. 1–241. Pergamon, Oxford
Nohmi, M., Kuba, K. 1984. (+)-Tubocurarine blocks the Ca(2+)dependent K(+)-channels of the bullfrog sympathetic ganglia cell. Brain Res. 301:146–148
Pauling, P., Petcher, T.J. 1973. Neuromuscular blocking agents: structure and activity. Chem-Biol. Interact. 6:351–365
Rang, H.P. 1982. The action of ganglionic blocking drugs on the synaptic responses at rat submandibular ganglion cells. Brit. J. Pharmacol. 75:151–168
Reynolds, C.D., Palmer, R.A. 1976. The crystal structure, absolute configuration and stereochemistry of (+)-tubocurarine dibromide methanol solvate: a potent neuromuscular blocking agent. Acta Ctystallogr. B32:1431–1439
Selyanko, A.A., Derkach, V.A., Kurenny, D.E., Skok, V.I. 1988. Mechanism of the tubocurarine action on nicotinic acetylcholine receptors in superior cervical ganglion neurons of rat. Neurophysiology 20:672–680 (in Russian)
Sobell, H.M., Sakore, T.D., Tavale, S.S., Canepa, F.G., Pauling, P., Petcher, T.J. 1972. Stereochemistry of a curare alkaloid: O,O′,N-trimethyl-d-tubocurarine. Proc. Natl. Acad. Sci. USA 69:2212–2215
Voitenco, S., Purnyn, S., Omelchenco, I., Dyadyusha, G., Zhorov, B., Brovtsyna, N., Skok, V. 1991. Effect of sparteine on nicotinic acetylcholine receptors in the neurons of rat superior cervical ganglion. Mol. Pharmacol. 10:180–185
Wiberg, K.B., Boyd, R.H. 1972. Application of strain energy minimization to the dynamics of conformational changes. J. Am. Chem. Soc. 94:8426–8430
Yamamoto, D., Washio, H. 1979. Curare has a voltage-dependent blocking action on the glutamate synapse. Nature 281:372–3
Zhorov, B.S. 1975. Computer modeling of the three-dimensional structures of organic compounds. Avtometriya N1::23–29 (in Russian)
Zhorov, B.S., Brovtsyna, N.B., Gmiro, V.E., Lukomskaya, N.Ya., Serdyuk, S.E., Potapyeva, N.N., Magazanik, L.G., Kurenniy, D.E., Skok, V.I. 1991. Dimensions of the ion channel in neuronal nicotinic acetylcholine receptor as estimated from analysis of conformation-activity relationships of open channel blocking drugs. J. Membrane Biol. 121:117–130
Zhorov, B.S., Govyrin, V.A. 1979. Relationship between spatial structure and pharmacological activity of a series of beta-adrenomimetics. Int. J. Quant. Chem. 16:517–525