Modeling of the recognition site of the NK1 receptor

Svein Saebo, Elizabeth Keene, Tammy Fang, Bert C. Lynn, Rickey P. Hicks

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The tachykinin receptor, NK1, and its native neuropeptide ligand, substance P, are believed to play a major role in the biochemistry of inflammation and in the transmission of pain. The binding of substance P is known to involve extracellular as well as transmembrane regions of the NK1 receptor. Reported here is the design of a model of the recognition site of the second transmembrane domain of the NK1 receptor. Molecular mechanics calculations were employed to evaluate the potential of six polypeptides corresponding to the first, second and third transmembrane domains of the NK1 receptor, to bind with substance P. One of the most promising of these models contained 30 amino acid residues corresponding to part of the first extracellular region coupled to the second transmembrane domain. A model of reduced size (18 amino acid residues) that contains the correct type and location of the amino acid residues predicted to be involved in ligand binding was used to validate the results of the molecular mechanics calculations. One-dimensional proton NMR spectra acquired in DMSO-d6 indicated that this 18 amino acid residue polypeptide forms a complex with substance P.

Original languageEnglish (US)
Pages (from-to)65-77
Number of pages13
JournalJournal of Molecular Structure: THEOCHEM
Volume366
Issue number1-2
DOIs
StatePublished - Jul 31 1996

Fingerprint

Substance P
amino acids
Amino Acids
Molecular mechanics
polypeptides
Mechanics
Tachykinin Receptors
Ligands
Peptides
biochemistry
ligands
Biochemistry
pain
Dimethyl Sulfoxide
Neuropeptides
Protons
Nuclear magnetic resonance
Inflammation
Pain
nuclear magnetic resonance

Keywords

  • Molecular mechanics calculation
  • Recognition site
  • Tachykinin receptor
  • Transmembrane domain

ASJC Scopus subject areas

  • Biochemistry
  • Condensed Matter Physics
  • Physical and Theoretical Chemistry

Cite this

Modeling of the recognition site of the NK1 receptor. / Saebo, Svein; Keene, Elizabeth; Fang, Tammy; Lynn, Bert C.; Hicks, Rickey P.

In: Journal of Molecular Structure: THEOCHEM, Vol. 366, No. 1-2, 31.07.1996, p. 65-77.

Research output: Contribution to journalArticle

Saebo, S, Keene, E, Fang, T, Lynn, BC & Hicks, RP 1996, 'Modeling of the recognition site of the NK1 receptor', Journal of Molecular Structure: THEOCHEM, vol. 366, no. 1-2, pp. 65-77. https://doi.org/10.1016/0166-1280(96)04552-6
Saebo, Svein ; Keene, Elizabeth ; Fang, Tammy ; Lynn, Bert C. ; Hicks, Rickey P. / Modeling of the recognition site of the NK1 receptor. In: Journal of Molecular Structure: THEOCHEM. 1996 ; Vol. 366, No. 1-2. pp. 65-77.
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