Fig. 7: Putative flexibility-based mechanism of electron transport in STEAP4.

Cutaway view of a wing of the STEAP4 molecule (6hcy). Representation as in Fig. 6 except for colour: for chain A, protein carbon atoms are shown in green, and non-protein carbon atoms are pink; atoms are otherwise coloured by element. a Deposited B-factors. The electron transport pathway in STEAP4 requires the transfer of a hydride ion from the bound NADPH molecule to the FAD molecule, which subsequently transfers two electrons to the heme molecule, which subsequently reduces bound substrate molecules, Fe³⁺/Cu²⁺ ions. The pathway for transfer of the hydride from the NADPH molecule to the FAD molecule is unknown¹⁹. b ECHT secondary-structure level. The observed flexibility suggests a mechanism whereby shuttling of the FAD molecule, caused by breathing of the flexible wing, brings the FAD flavin moiety in close proximity to the NADPH, where it can gain the hydride, and then subsequently transfer electrons to the heme molecule upon returning to the solved state. c The residue level reveals that the FAD molecule has increased disorder relative to its surroundings, further suggesting that structural transitions could be possible. Images rendered in pymol²⁹.