The tyrosine phosphatase SHP2 interconverts between open, active, and closed, inactive, structures to regulate crucial cell signaling pathways. Oncogenic mutations such as E76K shifts the equilibrium towards the open state making SHP2 200 fold more active than WT. In contrast to the closed state of SHP2 that has been well described mainly by crystal structures, the open structure is unknown and possibly adopts a ensemble of states in solution that hampers crystallization. Using homology modeling...

Glucosinolates, a group of sulfur-rich thioglucosides found in plants of the order Brassicales, have attracted a lot of interest as chemical defenses of plants and health promoting substances in human diet. They are accumulated separately from their hydrolyzing enzymes, myrosinases, within the intact plant, but undergo myrosinase-catalyzed hydrolysis upon tissue disruption. This results in various biologically active products, e.g. isothiocyanates, simple nitriles, epithionitriles, and organic thiocyanates. While formation of isothiocyanates proceeds by a spontaneous rearrangement...

Catecholamine neurotransmitter levels in the synapses of the brain shape human disposition — cognitive flexibility, aggression, depression, reward seeking… — and manipulating these levels is a major objective of the pharmaceutical industry. Certain transmitters are extensively sulfonated — an inactivating modification catalyzed by human sulfotransferase 1A3 (SULT1A3). To our knowledge, sulfonation as therapeutic means of regulating transmitter activity has not been explored. Here we describe the discovery of a SULT1A3 allosteric site that can be...