Work

Allosteric Functional Switch of Neurokinin A-Mediated Signaling at the Neurokinin NK2 Receptor: Structural Exploration

Year: 2009

Type: article

Abstract: The neurokinin NK2 receptor is known to pre-exist in equilibrium between at least three states: resting-inactive, calcium-triggering, and cAMP-producing. Its endogeneous ligand, NKA, mainly induces the calcium response. Using a FRET-based assay, we have previously discovered an allosteric modulator of the NK2 receptor that has the unique ability to discriminate among the two signaling pathways: calcium-signaling is not affected while cAMP signaling is significantly decreased. A series of compounds have been prepared and studied in order to better understand the structural determinants of this allosteric functional switch of a GPCR. Most of them display the same allosteric profile, with smooth pharmacomodulation. One compound however exhibits significantly improved modulatory properties of NKA induced signaling when compared to the original modulator.

Source: Journal of Medicinal Chemistry

DOI: 10.1021/jm900671k

Authors: Céline Valant, Emeline Maillet, Jean-Jacques Bourguignon, Bernard Bucher, Valérie Utard, Jean-Luc Galzi, Marcel Hibert

Institutions: Centre National de la Recherche Scientifique, Laboratoire d'Innovation Thérapeutique, Université de Strasbourg, École Supérieure de Biotechnologie de Strasbourg, Laboratoire de Biophotonique et Pharmacologie

Language: English

Topic: Receptor Mechanisms and Signaling

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

OpenAlex ID: W2010182386

FWCI: 0.668

Cites: 32

Cited by: 16

Related to: 10