The crystal structure of transhydrogenase (TH) shows two copies of the molecule, each of which contains three domains: domain I, domain II and domain III. Black spheres in domain III represent NADP(H). Structural asymmetry is observed in domain III: one is facing up (green) to catalyze the production of NADPH; the other is facing down (magenta) towards the transmembrane domain II to facilitate the transit of a proton. Labels “in” and “out” respectively denote mitochondrial matrix or the space outside the inner mitochondrial membrane. (Image by Josephine H. Leung, TSRI Stout lab.)