3.A.1.129.1
Heme transporter (previously proposed to be a thiol (cysteine/glutathione) exporter, CydDC; CydC is also called MdrH (periplasmic cysteine is required for cytochrome bd assembly) (Cruz-Ramos et al., 2004).  The purified asymmetric heterodimer exhibits low ATPase activity which is activated by both thiols and heme (e.g., heme b) (Yamashita et al. 2014).  Bacterial redox homoeostasis during nitrosative stress is influenced by CydDC.  Periplasmic low molecular weight thiols restore haem incorporation into a cytochrome complex (Holyoake et al. 2016). Iron-bound cyclic tetrapyrroles (hemes) are redox-active cofactors in bioenergetic enzymes. Wu et al. 2023 used cellular, biochemical, structural and computational methods to characterize CydDC which is a heme transporter required for functional maturation of cytochrome bd. The conformational landscape of CydDC during substrate binding and occlusion was revealed. Heme binds laterally from the membrane space to the transmembrane region of CydDC, enabled by a highly asymmetrical inward-facing CydDC conformation. During the binding process, heme propionates interact with positively charged residues on the surface and later in the substrate-binding pocket of the transporter, causing the heme orientation to rotate 180° (Wu et al. 2023).