RSAD1 is a heme chaperone catalyzing the insertion of heme into hemoproteins

There seems to be a chaperone protein in bacteria that inserts heme into heme-proteins.

This chaperone requires SAMe, but not for methylation - it’s a radical SAMe enzyme (SAMe will be “destroyed”).

Humans have similar enzyme called RSAD1.

Implications of this: if insertion of heme into heme-proteins depends on SAMe availability (especially in mitochondria), that has a direct and profound effect on bioenergetics of the cells, because heme is widely used in proteins that are involved in energy production, including electron transport chain.

As other radical SAM proteins, HemW contains three cysteines and one SAM coordinating an [4Fe-4S] cluster, and we observed one heme per subunit of HemW.

We found that an intact iron-sulfur cluster was required for HemW dimerization and HemW-catalyzed heme transfer but not for stable heme binding.

Finally, the human HemW orthologue radical SAM domain-containing 1 (RSAD1) stably bound heme. In conclusion, our findings indicate that the radical SAM protein family HemW/RSAD1 is a heme chaperone catalyzing the insertion of heme into hemoproteins. (R1)