2015
DOI: 10.1016/j.ejps.2015.05.005
|View full text |Cite
|
Sign up to set email alerts
|

Biomolecular recognition of antagonists by α7 nicotinic acetylcholine receptor: Antagonistic mechanism and structure–activity relationships studies

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
2
1

Citation Types

2
4
0

Year Published

2018
2018
2023
2023

Publication Types

Select...
4
1

Relationship

0
5

Authors

Journals

citations
Cited by 5 publications
(6 citation statements)
references
References 81 publications
2
4
0
Order By: Relevance
“…Another region that exhibits marginally higher RMSF for amidated LsIA-bound α7 is the loop C region, which forms part of the canonical agonist binding site and, in the α-subunits of nAChRs, is composed of a β hairpin with a twin Cys motif at the edge of the loop. This enhanced fluctuation is in accordance with previous studies on nAChRs, including those for apo α7 and α7-antagonist-bound complexes [53]. Nonetheless, the higher RMSF of both loop C and the juxtamembrane Cys-loop region, for amidated LsIA, is consistent with the present notion that movements in these two areas are strongly coupled, and is required for transmission of structural effects due to agonist (or antagonist) binding from the ECD to the transmembrane pore.…”
Section: Resultssupporting
confidence: 93%
See 1 more Smart Citation
“…Another region that exhibits marginally higher RMSF for amidated LsIA-bound α7 is the loop C region, which forms part of the canonical agonist binding site and, in the α-subunits of nAChRs, is composed of a β hairpin with a twin Cys motif at the edge of the loop. This enhanced fluctuation is in accordance with previous studies on nAChRs, including those for apo α7 and α7-antagonist-bound complexes [53]. Nonetheless, the higher RMSF of both loop C and the juxtamembrane Cys-loop region, for amidated LsIA, is consistent with the present notion that movements in these two areas are strongly coupled, and is required for transmission of structural effects due to agonist (or antagonist) binding from the ECD to the transmembrane pore.…”
Section: Resultssupporting
confidence: 93%
“…These plots demonstrate the greatest flexibility in the Cys-loop, and are similar to the RMSF results of several previous studies, such as that of α-ImI bound form, by Yu et al via computational simulations [18], who found that the Cys-loop RMSF increased compared with apo human α7 nAChR. There is also relatively high flexibility of β1/β2 loop and β10 strand, similar to previous studies [53].…”
Section: Resultssupporting
confidence: 88%
“…Neuronal nAChRs also are expressed in numerous other cell types and tissues, including endothelial cells, gastrointestinal tissues, glia, immune cells, keratinocytes, urinary bladder tissues, reproductive organs, and respiratory tissues [ 85 - 96 ]. In addition to the acetylcholine binding sites [ 20 , 40 ] other binding sites on nAChRs, such as the cholesterol-binding sites in M1–M4 segments [ 74 , 97 ] the α-neurotoxin-binding sites in the central loop C of the α subunit, [ 98 ] and binding sites for methyllycaconitine and synthetic antagonists [ 99 ] have been identified. As a result of their roles in the propagation of action potentials, cognitive function, and diverse central nervous system pathologies, they are hypothetical targets for many drugs and toxins [ 84 , 100 ].…”
Section: The Structure and Diversity Of Nachrsmentioning
confidence: 99%
“…This pharmacophore includes a basic amine protonated at physiological pH for cation−π interaction, a hydrophobic aromatic part for π–π interaction, and a linker that acts as a hydrogen bond acceptor (Figure ). Peng et al reported that hydrogen bonds, π–π interactions, and hydrophobic interactions are important binding interactions for α7 nAChR antagonists . Further, they identified specific amino acid residues involved in the interaction with the antagonist from in silico systems, such as Tyr93, Lys143, Trp147, Tyr188, and Tyr195 in the principal subunit as well as Trp55 and Leu118 in the complementary subunit.…”
Section: The Development Of α7 Nicotinic Acetylcholine Receptor Antag...mentioning
confidence: 99%
“…64 Peng et al reported that hydrogen bonds, π−π interactions, and hydrophobic interactions are important binding interactions for α7 nAChR antagonists. 65 Further, they identified specific amino acid residues involved in the interaction with the antagonist from in silico systems, such as Tyr93, Lys143, Trp147, Tyr188, and Tyr195 in the principal subunit as well as Trp55 and Leu118 in the complementary subunit. The most crucial residues for antagonist recognition were Ty93, Trp147, and Tyr188 in the principal subunit, as determined by site-directed α7 nAChR mutagenesis.…”
Section: ■ the Development Of α7 Nicotinic Acetylcholine Receptor Ant...mentioning
confidence: 99%