Human citrate synthase kinetic simulation to fit rapid, direct, and thiol probe coupled kinetic data.

Human citrate synthase (hCS) was kinetically characterized through full progress curve kinetic modelling using kinetic simulation, global fitting of the direct AcCoA to CoA transition, and a coupled thiol probe reaction to better determine the kinetics with low substrate concentration. Our analysis provides one of the most rigorous kinetic analyses of any citrate synthase ruling out the need to invoke complex cooperative mechanisms to explain progress curve data. Furthermore, we collected and modeled stopped-flow pH-dependent kinetic data with CoA and popular thiol probes such as Ellman's reagent (DTNB) and 4,4'-Dithiodipyridine (DPS), providing the opportunity for detailed kinetic simulations using these thiol probes with CoA producing enzymes.

Evaluation of Rhodanine Indolinones as AANAT Inhibitors.

Circadian rhythm (CR) dysregulation negatively impacts health and contributes to mental disorders. The role of melatonin, a hormone intricately linked to CR, is still a subject of active study. The enzyme arylalkylamine N-acetyltransferase (AANAT) is responsible for melatonin synthesis, and it is a potential target for disorders that involve abnormally high melatonin levels, such as seasonal affective disorder (SAD).