Journal article
Characterization of d-tubocurarine binding site of Torpedo acetylcholine receptor
American Journal of Physiology: Cell Physiology, v 266(3), pp C648-C653
01 Mar 1994
PMID: 8166227
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Abstract
d-Tubocurarine (curare) is a well-characterized competitive antagonist of nicotinic acetylcholine receptors (AChRs), and it is usually assumed that curare and agonists share a common binding site. We have examined the role of several highly conserved residues of the alpha-, gamma-, and delta-subunits in the interaction of curare with the Torpedo acetylcholine receptor (AChR). Curare inhibition of wild-type receptors is consistent with curare binding to a single high-affinity binding site [inhibitor constant (Ki) = 20 nM]. Phenylalanine substitutions for two tyrosine residues implicated as being in the ligand binding site (alpha Y93F, alpha Y190F) reduce curare affinity, indicating that these residues are also important for high-affinity curare binding. Phenylalanine substitution for alpha Y198 [alpha Y198F (notation used here: subunit/amino acid in wild-type/residue number/substitution)] causes a 10-fold increase in curare affinity (Ki = 3.1 nM), and measurement of the recovery from curare inhibition indicates that this increase in affinity is due to a reduction in the rate of curare dissociation from the receptor. In addition to the alpha-subunits, portions of the ligand binding sites also reside on the gamma- and delta-subunits, and photoaffinity studies have implicated two residues (gamma W55 and delta W57) as forming part of the curare sites. The gamma W55L mutation results in an eightfold decrease in curare affinity (Ki = 170 nM), whereas the delta W57L mutation has no effect. These data support the notion that the high-affinity curare binding site is formed by segments of the alpha- and gamma-subunits.
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Details
- Title
- Characterization of d-tubocurarine binding site of Torpedo acetylcholine receptor
- Creators
- M. E O'Leary - Department of Physiology, Medical College of Pennsylvania,Philadelphia 19129G. N Filatov - Department of Physiology, Medical College of Pennsylvania,Philadelphia 19129M. M White - Department of Physiology, Medical College of Pennsylvania,Philadelphia 19129
- Publication Details
- American Journal of Physiology: Cell Physiology, v 266(3), pp C648-C653
- Publisher
- American Physiological Society (APS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:A1994NF85900008
- Scopus ID
- 2-s2.0-0028316086
- Other Identifier
- 991014877767704721
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- Web of Science research areas
- Physiology