Journal:JBIC:4

Bacterial ferrochelatase turns human: Tyr13 determines the apparent metal specificity of Bacillus subtilis ferrochelatase

Mattias D. Hansson • Tobias Karlberg • Christopher A. G. So ̈derberg • Sreekanth Rajan • Martin J. Warren • Salam Al-Karadaghi • Stephen E. J. Rigby • Mats Hansson^[1]

Molecular Tour

Ferrochelatase produces heme by insertion of iron into protoporphyrin IX. It can also insert other metal ions. However, the ability to insert other metal ions is species specific. In this way Bacillus subtilis ferrochelatase can insert copper into protoporphyrin IX, but to a much less extent cobalt. In contrast, the human and Saccharomyces cerevisiae ferrochelatases prefer cobalt over copper. Our structural work shows that one His residue and one Glu residue are direct ligands to the metal ion, while A third residue, Tyr in B. subtilis, is a third ligand via a water molecule. Human and S. cerevisiae ferrochelatase utilizes Met as a third residue to bind the metal ligand. In the structures of the ferrochelatases the Tyr/Met occupies the same position. We also know that the Tyr residue of the B. subtilis enzyme is a direct ligand to a copper-porphyrin reaction product. By site directed mutagenesis we changed the Tyr to a Met residue and showed that the metal specificity changed so that the modified B. subtilis ferrochelatase preferred cobalt over copper. Two crystal structures are presented. One shows how a metal ion (iron) is coordinated in the active site of the ''B. subtilis'' ferrochelatase. The other shows how a copper in a reaction product (copper-mesoporphyrin) is coordinated by the Tyr residue in the B. subtilis enzyme.

PDB references: Bacillus subtilis ferrochelatase, 3m4z; Crystal structure of the Tyr13Met variant of Bacillus subtilis ferrochelatase, 3goq.

References

1. ↑ Hansson MD, Karlberg T, Soderberg CA, Rajan S, Warren MJ, Al-Karadaghi S, Rigby SE, Hansson M. Bacterial ferrochelatase turns human: Tyr13 determines the apparent metal specificity of Bacillus subtilis ferrochelatase. J Biol Inorg Chem. 2010 Nov 4. PMID:21052751 doi:10.1007/s00775-010-0720-4