Linked Life Data

8166227

Source:http://linkedlifedata.com/resource/pubmed/id/8166227

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3 Pt 1
pubmed:dateCreated
1994-5-20
pubmed:abstractText
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.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0002-9513
pubmed:author
pubmed:issnType
Print
pubmed:volume
266
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
C648-53
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Characterization of d-tubocurarine binding site of Torpedo acetylcholine receptor.
pubmed:affiliation
Department of Physiology, Medical College of Pennsylvania, Philadelphia 19129.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.