Journal:JBIC:4

<applet load="2l0u" size="600" color="" frame="true" spin="on" Scene ="Journal:JBIC:4/Heme_bound_ferro_open/3" align="right" caption="Solved Crystal Structure of Ferrochelatase Mutant"/>

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

<big>Mattias D. Hansson • Tobias Karlberg • Christopher A. G. So ̈derberg • Sreekanth Rajan • Martin J. Warren • Salam Al-Karadaghi • Stephen E. J. Rigby • Mats Hansson</big>

Ferrochelatase produces <scene name='Journal:JBIC:4/Heme_bound_ferro/5'>heme by insertion of iron into protoporphyrin IX</scene>. It can also <scene name='Journal:JBIC:4/Copper_protorphyrin/4'>insert other metal ions</scene>. However, the ability to insert other <scene name='Journal:JBIC:4/Bound_cu_por/5'>metal ions is species specific</scene>. In this way ''Bacillus subtilis'' ferrochelatase can <scene name='Journal:JBIC:4/Bound_cu_por/4'>insert copper into protoporphyrin IX</scene>, but to a much less extent cobalt. In contrast, the human and ''Saccharomyces cerevisiae'' ferrochelatases prefer cobalt over copper. Our structural work shows that <scene name='Journal:JBIC:4/Iron_binding/9'>one His residue and one Glu residue are direct ligands to the metal ion</scene>, while A third residue, Tyr in ''B. subtilis'', is a third ligand via a water molecule. Human/''S. cerevisiae''' ferrochelatase utilizes <scene name='Journal:JBIC:4/Iron_bound_met/2'>Met as a third residue to bind the metal ligand.</scene> In the structures of the ferrochelatases the Tyr/Met occupies the same position. We also know that the Tyr residue of the <scene name='Journal:JBIC:4/Bound_cu_por/5'>B. subtilis enzyme</scene> is a <scene name='Journal:JBIC:4/Bound_cu_por/4'>direct ligand to a copper-porphyrin reaction product</scene>. 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. <scene name='Journal:JBIC:4/Iron_binding_zoomout/3'>One shows</scene> how <scene name='Journal:JBIC:4/Iron_binding_zoomout/1'>a metal ion (iron) is coordinated in the active site of the ''B. subtilis'' ferrochelatase</scene>. The <scene name='Journal:JBIC:4/Bound_cu_por/5'>other shows</scene> how a <scene name='Journal:JBIC:4/Bound_cu_por/4'>copper in a reaction product (copper-mesoporphyrin) is coordinated by the Tyr residue</scene> in the B. subtilis enzyme.