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 • 5 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 metal ions is species specific. In this way Bacillus subtilis <scene name='Journal:JBIC:4/Co_chelo_bound_open/1'>ferrochelatase </scene> can insert copper,<scene name='Journal:JBIC:4/Co_chelo_bound/3'> but to a much less extent cobalt</scene>. In contrast, the human and Saccharomyces cerevisiae <scene name='Journal:JBIC:4/Iron_binding_zoomout/2'>ferrochelatases</scene> prefer cobalt over copper. <scene name='Journal:JBIC:4/Iron_binding/9'>Our structural work shows that one His residue and one Glu residue are direct ligands to the metal ion</scene>. A third residue, <scene name='Journal:JBIC:4/Iron_bound_met/2'>Tyr in B. subtilis ferrochelatase and Met in human/S. cerevisiae ferrochelatase,</scene> is a third ligand via a water molecule. 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. <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/3'>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.