Structural basis of ligand recognition in 5‐HT<sub>3</sub> receptors

Kesters, Divya; Thompson, Andrew; Brams, Marijke; Elk, René van; Spurný, Radovan; Geitmann, Matthis; Villalgordo, José M.; Guskov, Albert; Danielson, U. Helena; Lummis, Sarah C. R.; Smit, August B.; Ulens, Chris

doi:10.1038/embor.2012.189

Cited by 76 publications

(136 citation statements)

References 18 publications

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“…It is well established that residues around ligand binding sites and those that form the aromatic box in Cys-loop family receptors often make cation-bonds with their cognate ligands (73). The reverse situation, when aromatic moieties of ligands engage in a cation-bond formation with positively charged residues of the receptor, is also possible (74). AuIB does not have positively charged residues so cannot make a cationbond with ␤4-Trp-59 (TrpD).…”

Section: The Role Of the ␤4 Nachr Loop D And Its Conserved Tryptophanmentioning

confidence: 99%

Identifying Key Amino Acid Residues That Affect α-Conotoxin AuIB Inhibition of α3β4 Nicotinic Acetylcholine Receptors

Grishin

Cuny

Hung

et al. 2013

Journal of Biological Chemistry

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Background: ␣-Conotoxin AuIB interacts with ␣3␤4 nAChRs and GABA B receptors, but structural determinants of these interactions are unknown. Results: Using alanine scanning mutagenesis and molecular dynamics, we identified residues crucial for AuIB⅐␣3␤4 nAChR interaction. Conclusion:We identified the key residues that mediate AuIB⅐␣3␤4 nAChR interaction. Significance: Ability to direct ␣-conotoxin binding to nAChRs or GABA B receptors will improve analgesic conopeptides.

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Section: The Role Of the ␤4 Nachr Loop D And Its Conserved Tryptophanmentioning

confidence: 99%

Identifying Key Amino Acid Residues That Affect α-Conotoxin AuIB Inhibition of α3β4 Nicotinic Acetylcholine Receptors

Grishin

Cuny

Hung

et al. 2013

Journal of Biological Chemistry

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“…Furthermore, 5F-ADB has an indazole structure (Fig. 1), which is common among ligands for several serotonin receptors, such as 5-HT 3 receptors (Kesters et al, 2013), raising the possibility that 5F-ADB affects serotonergic neuronal activity via interactions with serotonin receptors.…”

Section: Introductionmentioning

confidence: 99%

A new designer drug 5F-ADB activates midbrain dopaminergic neurons but not serotonergic neurons

et al. 2016

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-N-[[1-(5-fluoropentyl)-1H-indazol-3-yl]carbonyl]-3-methyl-D-valine methyl ester (5F-ADB) is one of the most potent synthetic cannabinoids and elicits severe psychotic symptoms in humans, sometimes causing death. To investigate the neuronal mechanisms underlying its toxicity, we examined the effects of 5F-ADB on midbrain dopaminergic and serotonergic systems, which modulate various basic brain functions such as those in reward-related behavior. 5F-ADB-induced changes in spontaneous firing activity of dopaminergic and serotonergic neurons were recorded by ex vivo electrophysiological techniques. In dopaminergic neurons, 5F-ADB (1 μM) significantly increased the spontaneous firing rate, while 5F-ADB failed to activate dopaminergic neurons in the presence of the CB 1 antagonist AM251 (1 μM). However, the same concentration of 5F-ADB did not affect serotonergic-neuron activity. These results suggest that 5F-ADB activates local CB 1 receptors and potentiates midbrain dopaminergic systems with no direct effects on midbrain serotonergic systems.

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“…The data suggest that the granisetron binding pocket is less sterically confined around the N(1) nitrogen and thus this position is more likely to accommodate bulky modifications. [12] …”

Section: Resultsmentioning

confidence: 99%

Synthesis and Characterization of Photoaffinity Probes that Target the 5-HT3 Receptor

Jack

Ruepp

Thompson

et al. 2014

Chimia

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Abstract:The 5-HT 3 receptor is one of several ion channels responsible for the transmission of nerve impulses in the peripheral and central nervous systems. Until now, it has been difficult to characterize transmembrane receptors with classical structural biology approaches like X-ray crystallography. The use of photoaffinity probes is an alternative approach to identify regions in the protein where small molecules bind. To this end, we present two photoaffinity probes based on granisetron, a well known antagonist of the 5-HT 3 receptor. These new probes show nanomolar binding affinity for the orthosteric binding site. In addition, we investigated their reactivity using irradiation experiments.

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Structural basis of ligand recognition in 5‐HT₃ receptors

Cited by 76 publications

References 18 publications

Identifying Key Amino Acid Residues That Affect α-Conotoxin AuIB Inhibition of α3β4 Nicotinic Acetylcholine Receptors

Identifying Key Amino Acid Residues That Affect α-Conotoxin AuIB Inhibition of α3β4 Nicotinic Acetylcholine Receptors

A new designer drug 5F-ADB activates midbrain dopaminergic neurons but not serotonergic neurons

Synthesis and Characterization of Photoaffinity Probes that Target the 5-HT3 Receptor

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Structural basis of ligand recognition in 5‐HT3 receptors

Cited by 76 publications

References 18 publications

Identifying Key Amino Acid Residues That Affect α-Conotoxin AuIB Inhibition of α3β4 Nicotinic Acetylcholine Receptors

Identifying Key Amino Acid Residues That Affect α-Conotoxin AuIB Inhibition of α3β4 Nicotinic Acetylcholine Receptors

A new designer drug 5F-ADB activates midbrain dopaminergic neurons but not serotonergic neurons

Synthesis and Characterization of Photoaffinity Probes that Target the 5-HT3 Receptor

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Structural basis of ligand recognition in 5‐HT₃ receptors