14 research outputs found
A dual inhibitor of matrix metalloproteinases and a disintegrin and metalloproteinases, [F-18]FB-ML5, as a molecular probe for non-invasive MMP/ADAM-targeted imaging
Bio-organic Synthesi
Impact of composted guava leaves and neem seeds on the growth and curcuminoid- and xanthorrhizol-yields of Curcuma zanthorrhiza RoxB
Evaluation of anti-inflammatory effects of polyherbal decoction, balaguluchyadi kashayam
Renal Cyclooxygenase Products are Higher and Lipoxygenase Products are Lower in Early Disease in the pcy Mouse Model of Adolescent Nephronophthisis
Uncoupling conformational states from activity in an allosteric enzyme
ATP-phosphoribosyltransferase (ATP-PRT) is a hexameric enzyme in conformational equilibrium between an open and seemingly active state and a closed and presumably inhibited form. The structure-function relationship of allosteric regulation in this system is still not fully understood. Here, we develop a screening strategy for modulators of ATP-PRT and identify 3-(2-thienyl)-l-alanine (TIH) as an allosteric activator of this enzyme. Kinetic analysis reveals co-occupancy of the allosteric sites by TIH and l-histidine. Crystallographic and native ion-mobility mass spectrometry data show that the TIH-bound activated form of the enzyme closely resembles the inhibited l-histidine-bound closed conformation, revealing the uncoupling between ATP-PRT open and closed conformations and its functional state. These findings suggest that dynamic processes are responsible for ATP-PRT allosteric regulation and that similar mechanisms might also be found in other enzymes bearing a ferredoxin-like allosteric domain.</p