Figure 1

NMR-based ligand screening of MA4265, a putative isocitrate/isopropylmalate dehydrogenase. Part of the metabolic pathway involving isocitrate dehydrogenase functionality is shown at the top of the figure. The relevant section of the one-dimensional waterLOGSY ¹H NMR spectrum is shown for each metabolite (300 μM) in the presence of MA4265 (30 μM) as follows: (a) citrate; (b) cis-aconitate; (c) isocitrate; (d) 2-ketoglutarate; (e) control spectrum of MA4265 alone. Peaks due to each compound are labeled with asterisks. Metabolite interaction with MA4265 is represented as positive peaks whereas negative peaks indicate no binding to the protein. The negative peak at 3.4 ppm in all spectra is thought to be a contaminant from the protein concentration process. Only isocitrate binds to MA4265 under the conditions used.