On the basis of amino acid sequences and crystal structures of similar enzymes, it is proposed that Met95 of the heme-regulatedphosphodiesterase fromEscherichiacoli(EcDOS) acts as aheme axial ligand. Inaccordancewith this proposal, the Soret and visible optical absorption and magnetic circular dichroism spectra of the Fe(II) complexes of the Met95Ala and Met95Leu mutant proteins indicate that these complexes are five-coordinated high-spin, suggesting that Met95 is an axial ligand for the Fe(II) complex. .