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Theoretical Chemistry Accounts

, Volume 106, Issue 1–2, pp 98–104 | Cite as

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

  • Maria Cristina Menziani
  • Francesca De Rienzo
  • Andrea Cappelli
  • Maurizio Anzini
  • Pier G. De Benedetti
Regular article

Abstract.

A three-dimensional model of the 5-HT3 receptor extarcellular 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.

Key words: Molecular modelling 5-HT3 receptor Extracellular domain Ligand binding site Ligand-gated ion channel 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • Maria Cristina Menziani
    • 1
  • Francesca De Rienzo
    • 1
  • Andrea Cappelli
    • 2
  • Maurizio Anzini
    • 3
  • Pier G. De Benedetti
    • 1
  1. 1.Dipartimento di Chimica, Universita' di Modena e Reggio E., Via Campi 183, 41100 Modena, ItalyIT
  2. 2.Dipartimento Farmaco Chimico Tecnologico, Università di Siena, Via A. Moro, 53100 Siena, ItalyIT
  3. 3.Dipartimento di Scienze Farmaco-Biologiche, Università di Catanzaro “Magna Graecia”, Complesso Ninì Barbieri, 88021 Roccelletta di Borgia, Catanzaro, ItalyIT

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