Drugging Ras GTPase: a comprehensive mechanistic and signaling structural view

Structural and mechanistic insights into cGMP signaling

Background The second messenger cGMP plays a central role in regulating bodily functions, e.g. in the cardiovascular and nervous systems. cGMP is formed by guanylyl cyclases (GC), activates target proteins, and is finally hydrolyzed by cyclic nucleotide phosphodiesterases (PDE). PDEs and GCs are widely used as drug targets, spurring interest in mechanistic and structural insights into their reg...

Mental hospital drugging--atomistic and structural remedies.

The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants.

The three-dimensional structure of the complex between human H-Ras bound to guanosine diphosphate and the guanosine triphosphatase (GTPase)-activating domain of the human GTPase-activating protein p120GAP (GAP-334) in the presence of aluminum fluoride was solved at a resolution of 2.5 angstroms. The structure shows the partly hydrophilic and partly hydrophobic nature of the communication betwee...

Finding and Drugging the Vulnerabilities of RAS-Dependent Cancers

Kinase inhibitors have ushered in the era of targeted therapy, but their utility to date is primarily limited to cancers bearing oncogenic kinase mutations. Two papers in this issue (Luo et al., 2009; Scholl et al., 2009) could change this landscape by uncovering kinase-specific vulnerabilities in tumors with RAS mutations.

Opioid receptors: Structural and mechanistic insights into pharmacology and signaling.

Opioid receptors are important drug targets for pain management, addiction, and mood disorders. Although substantial research on these important subtypes of G protein-coupled receptors has been conducted over the past two decades to discover ligands with higher specificity and diminished side effects, currently used opioid therapeutics remain suboptimal. Luckily, recent advances in structural b...