Figure 6. Promiscuous nucleophilic addition and active site persulfide formation.

A, Alternative to sulfide, nucleophiles (Nuc) including GSH, sulfite, and methanethiol are capable of adding into the cysteine trisulfide to form a slowly decaying dead-end complex. The right panel (adapted from Ref. 93 Supplemental Figure 2) shows SQOR embedded in nanodiscs (20 μM, black trace) rapidly mixed with sulfite (500 μM) and monitored over a period of 14 s for the formation of an alternative CT complex (red trace), with an absorbance maximum at 675 nm. B, Active site of human SQOR co-crystallized with CoQ (orange sticks) and soaked with sulfite (PDB: 6OIC), which contained a stable ²⁰¹Cys persulfide-to-FAD CT complex in crystallo. C, Active site of ACADS crystallized with bound CoA persulfide (PDB: 2VIG), shown as blue sticks. In panels B and C, the sulfane sulfur in ²⁰¹Cys-SSH and in CoA-SSH persulfide are shown as yellow spheres.