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Three-Dimensional Structure of the Smoothened Receptor: Implications for Drug Discovery

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The Smoothened Receptor in Cancer and Regenerative Medicine

Part of the book series: Topics in Medicinal Chemistry ((TMC,volume 16))

Abstract

The recently described high resolution three-dimensional structures of the transmembrane and the extracellular domains of the human Smoothened (Smo) receptor higlight both conserved and unique structural features of this G protein-coupled receptor. It enables a better understanding of very subtle molecular mechanisms regulating Smo function and demonstrates the very plastic nature of this receptor which is able to accommodate a diverse array of small molecular weight ligands through several binding sites. This structural information should pave the way for designing small molecular weight modulators of Smo function targeting different binding sites and insensitive to clinically observed receptor mutations.

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Abbreviations

BCC:

Basal cell carcinoma

Bud:

Budesonide

drSmo:

Drosophila Smoothened

ECD:

Extracellular domain

ECD:

Cystein-rich domain

ECL:

Extracellular loop

GPCR:

G protein-coupled receptor

hSmo:

Human Smoothened

Hh:

Hedgehog

ICL:

Intracellular loop

NMR:

Nuclear magnetic resonance

Smo:

Smoothened

TM:

Transmembrane

zSmo:

Zebrafish Smoothened

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Authors and Affiliations

  1. Laboratoire d’Innovation Thérapeutique, UMR 7200 CNRS-Université de Strasbourg, F-67400, Illkirch, France

    Didier Rognan

  2. Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275 CNRS-Université de Nice-Sophia Antipolis, 67400, Illkirch, France

    Isabelle Mus-Veteau

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  1. Didier Rognan
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  2. Isabelle Mus-Veteau
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Correspondence to Didier Rognan .

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Editors and Affiliations

  1. Institute of Neurosciences Paris-Saclay (Neuro-PSI), National Centre for Scientific Research, Gif-Yvette, France

    Martial Ruat

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Rognan, D., Mus-Veteau, I. (2014). Three-Dimensional Structure of the Smoothened Receptor: Implications for Drug Discovery. In: Ruat, M. (eds) The Smoothened Receptor in Cancer and Regenerative Medicine. Topics in Medicinal Chemistry, vol 16. Springer, Cham. https://doi.org/10.1007/7355_2014_64

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