6FAE

The Sec7 domain of IQSEC2 (Brag1) in complex with the small GTPase Arf1

Summary for 6FAE

• Entry DOI: 10.2210/pdb6fae/pdb
• Descriptor: IQ motif and SEC7 domain-containing protein 2, ADP-ribosylation factor 1, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: gtpase gef, hydrolase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 67448.08

Authors

Gray, J.,Krojer, T.,Fairhead, M.,Bountra, C.,Arrowsmith, C.H.,Edwards, A.,Brennan, P.,von Delft, F. (deposition date: 2017-12-15, release date: 2018-01-17, Last modification date: 2024-05-08)

Primary citation

Gray, J.L.,von Delft, F.,Brennan, P.
Targeting the Small GTPase Superfamily through their Regulatory Proteins.
Angew.Chem.Int.Ed.Engl., 2019

PubMed Abstract: The Ras superfamily of small GTPases are guanine-nucleotide-dependent switches essential for numerous cellular processes. Mutations or dysregulation of these proteins are associated with many diseases, but unsuccessful attempts to target the small GTPases directly have resulted in them being classed as "undruggable". The GTP-dependent signaling of these proteins is controlled by their regulators; guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs), and in the Rho and Rab subfamilies, guanine nucleotide dissociation inhibitors (GDIs). This review covers the recent small molecule and biologics strategies to target the small GTPases through their regulators. It seeks to critically re-evaluate recent chemical biology practice, such as the presence of PAINs motifs and the cell-based readout using compounds that are weakly potent or of unknown specificity. It highlights the vast scope of potential approaches for targeting the small GTPases in the future through their regulatory proteins.

PubMed: 30869179
DOI: 10.1002/anie.201900585

Experimental method

X-RAY DIFFRACTION (2.35 Å)