G protein-coupled receptors: structure-and function-based drug discovery

D Yang, Q Zhou, V Labroska, S Qin… - Signal transduction and …, 2021 - nature.com
As one of the most successful therapeutic target families, G protein-coupled receptors
(GPCRs) have experienced a transformation from random ligand screening to knowledge …

Structure-based virtual screening for ligands of G protein–coupled receptors: what can molecular docking do for you?

F Ballante, AJ Kooistra, S Kampen, C de Graaf… - Pharmacological …, 2021 - Elsevier
G protein–coupled receptors (GPCRs) constitute the largest family of membrane proteins in
the human genome and are important therapeutic targets. During the last decade, the …

GPCR drug discovery: integrating solution NMR data with crystal and cryo-EM structures

I Shimada, T Ueda, Y Kofuku, MT Eddy… - Nature Reviews Drug …, 2019 - nature.com
The 826 G protein-coupled receptors (GPCRs) in the human proteome regulate key
physiological processes and thus have long been attractive drug targets. With the crystal …

Smoothened stimulation by membrane sterols drives Hedgehog pathway activity

I Deshpande, J Liang, D Hedeen, KJ Roberts, Y Zhang… - Nature, 2019 - nature.com
Hedgehog signalling is fundamental to embryonic development and postnatal tissue
regeneration. Aberrant postnatal Hedgehog signalling leads to several malignancies …

Cholesterol access in cellular membranes controls Hedgehog signaling

A Radhakrishnan, R Rohatgi, C Siebold - Nature chemical biology, 2020 - nature.com
Abstract The Hedgehog (Hh) signaling pathway coordinates cell–cell communication in
development and regeneration. Defects in this pathway underlie diseases ranging from birth …

Biochemical mechanisms of vertebrate hedgehog signaling

JH Kong, C Siebold, R Rohatgi - Development, 2019 - journals.biologists.com
Signaling pathways that mediate cell-cell communication are essential for collective cell
behaviors in multicellular systems. The hedgehog (HH) pathway, first discovered and …

Structural basis of smoothened activation in hedgehog signaling

P Huang, S Zheng, BM Wierbowski, Y Kim, D Nedelcu… - Cell, 2018 - cell.com
The seven-transmembrane-spanning protein Smoothened is the central transducer in
Hedgehog signaling, a pathway fundamental in development and in cancer. Smoothened is …

Fusion protein strategies for cryo-EM study of G protein-coupled receptors

K Zhang, H Wu, N Hoppe, A Manglik… - Nature …, 2022 - nature.com
Single particle cryogenic-electron microscopy (cryo-EM) is used extensively to determine
structures of activated G protein-coupled receptors (GPCRs) in complex with G proteins or …

A bright future for serial femtosecond crystallography with XFELs

LC Johansson, B Stauch, A Ishchenko… - Trends in biochemical …, 2017 - cell.com
X-ray free electron lasers (XFELs) have the potential to revolutionize macromolecular
structural biology due to the unique combination of spatial coherence, extreme peak …

Crystal structure of the Frizzled 4 receptor in a ligand-free state

S Yang, Y Wu, TH Xu, PW de Waal, Y He, M Pu… - Nature, 2018 - nature.com
Frizzled receptors (FZDs) are class-F G-protein-coupled receptors (GPCRs) that function in
Wnt signalling and are essential for develo** and adult organisms,. As central mediators …