Fabulous FabH
FabH catalyzes a key step in biosynthesis of mycolic acids, cell wall components of M. tuberculosis. Existing FabH structure suggests that the binding necessitates chain threading through a long and twisted passageway. Now Sachdeva et al. demonstrate that the FabH exists in an open form which permits binding and release of long carbon chain substrates without laborious twisting and threading.

Selected from the Pak
Lack of target specificity is a common drawback of kinase inhibitors that target the conserved ATP-binding pocket. Non-conserved regulatory elements found in some kinases may offer alternative targets for more selective kinase inhibition. Deacon et al. report the identification of IPA-3, a highly selective small-molecule inhibitor that targets the Pak kinase autoregulatory mechanism.

Breaking the Aminergic GPCRs Code
Despite the successful development of numerous drugs that can regulate the activity of aminergic G-protein coupled receptors (GPCRs), the underlying principles for developing activators and/or inhibitors are not well understood. Tan et al. now apply the rotamer toggle switch model of GPCR activation toward a design of agonists and antagonists of TAAR1, an orphan GPCR.

Ethylene Sensing in Plants
Ethylene, the simplest alkene, is a plant hormone, initially perceived by ethylene receptors, such as ETR1, via ethylene binding to a copper(I) cofactor in receptor’s sensor domain. Pirrung et al. now shed new light on the underlining principles of ethylene binding, as well as mechanism of action of 1-methylcylopropene, ETR1 antagonist that involves chemical modification of the receptor.