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Targeting Ras-, Rho-, and Rab-family GTPases via a conserved cryptic pocket

Cell. 2024-09; 
Johannes Morstein , Victoria Bowcut , Micah Fernando , Yue Yang , Lawrence Zhu , Meredith L Jenkins , John T Evans , Keelan Z Guiley , D Matthew Peacock , Sophie Krahnke , Zhi Lin , Katrine A Taran , Benjamin J Huang , Andrew G Stephen , John E Burke , Felice C Lightstone , Kevan M Shokat
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DNA Sequencing DNA sequences encoding human GTPases Cyslight (all C/S) were codon optimized, synthesized, and cloned into the pProEx vector by Genscript. Get A Quote

摘要

The family of Ras-like GTPases consists of over 150 different members, regulated by an even larger number of guanine exchange factors (GEFs) and GTPase-activating proteins (GAPs) that comprise cellular switch networks that govern cell motility, growth, polarity, protein trafficking, and gene expression. Efforts to develop selective small molecule probes and drugs for these proteins have been hampered by the high affinity of guanosine triphosphate (GTP) and lack of allosteric regulatory sites. This paradigm was recently challenged by the discovery of a cryptic allosteric pocket in the switch II region of K-Ras. Here, we ask whether similar pockets are present in GTPases beyond K-Ras. We systematically surveyed m... More

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