A three-dimensional model of the 5-HT3 receptor extracellular domain has been derived on the basis of the nicotinic acetylcholine receptor model recently published by Tsigelny et al. Maximum complementarity between the position and characteristics of mutated residues putatively involved in ligand interaction and the pharmacophoric elements derived by the indirect approach applied on several series of 5-HT3 ligands have been exploited to gain insights into the ligand binding modalities and to speculate on the mechanistic role of the structural components. The analysis of the three-dimensional model allows one to distinguish among amino acids that exert key roles in ligand interactions, subunit architecture, receptor assembly and receptor dynamics. For some of these, alternative roles with respect to the ones hypothesized by experimentalists are assigned. Different binding modalities for agonists and antagonists are highlighted, and residues which probably play a role in the transduction of binding into a change in conformational state of the receptor are suggested.

A computational model of the 5-HT3 receptor extracellular domain: search for ligand binding sites / Menziani, Maria Cristina; DE RIENZO, Francesca; A., Cappelli; M., Anzini; DE BENEDETTI, Pier Giuseppe. - In: THEORETICAL CHEMISTRY ACCOUNTS. - ISSN 1432-881X. - STAMPA. - 106(2001), pp. 98-104.

A computational model of the 5-HT3 receptor extracellular domain: search for ligand binding sites

MENZIANI, Maria Cristina;DE RIENZO, Francesca;DE BENEDETTI, Pier Giuseppe
2001

Abstract

A three-dimensional model of the 5-HT3 receptor extracellular domain has been derived on the basis of the nicotinic acetylcholine receptor model recently published by Tsigelny et al. Maximum complementarity between the position and characteristics of mutated residues putatively involved in ligand interaction and the pharmacophoric elements derived by the indirect approach applied on several series of 5-HT3 ligands have been exploited to gain insights into the ligand binding modalities and to speculate on the mechanistic role of the structural components. The analysis of the three-dimensional model allows one to distinguish among amino acids that exert key roles in ligand interactions, subunit architecture, receptor assembly and receptor dynamics. For some of these, alternative roles with respect to the ones hypothesized by experimentalists are assigned. Different binding modalities for agonists and antagonists are highlighted, and residues which probably play a role in the transduction of binding into a change in conformational state of the receptor are suggested.
106
98
104
A computational model of the 5-HT3 receptor extracellular domain: search for ligand binding sites / Menziani, Maria Cristina; DE RIENZO, Francesca; A., Cappelli; M., Anzini; DE BENEDETTI, Pier Giuseppe. - In: THEORETICAL CHEMISTRY ACCOUNTS. - ISSN 1432-881X. - STAMPA. - 106(2001), pp. 98-104.
Menziani, Maria Cristina; DE RIENZO, Francesca; A., Cappelli; M., Anzini; DE BENEDETTI, Pier Giuseppe
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/306699
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 14
  • ???jsp.display-item.citation.isi??? 14
social impact