Fission yeast Dap1 heme iron-coordinating residue Y83 is required for cytochromes P450 function

Fission yeast Dap1 is a heme binding protein required for cytochromes P450 activity. Here, we tested whether Dap1 axial coordination of heme iron is required for its role in the function of the cytochrome P450 enzymes, Erg5 and Erg11. Two different dap1 mutants predicted to alter iron coordination failed to rescue growth on cobalt chloride containing medium which requires Erg5 and Erg11. In addition, deletion of dap1 (+) did not affect expression of Erg5 or Erg11. PGRMC1, a mammalian Dap1 homolog, does not require heme binding to bind and stabilize cytochromes P450. These experiments highlight important functional differences between these conserved proteins.