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Ferrochelatase

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<StructureSection load='2qd2' size='450' side='right' scene='Journal:JBIC:4/Heme_bound_ferro_open/3' caption=''>
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<StructureSection load='1c1h' size='350' side='right' scene='52/526342/Cv/1' caption='Ferrochelatase with methylmesoporphyrin and Mg+2 ion (PDB code [[1c1h]])'>
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'''Ferrochelatase''' (FECH) catalyzes the last step in the formation of heme. FECH adds Fe+2 to protoporphyrin IX converting it to protoheme. The human FECH is a homodimer containing 2 similar domains and an iron-sulfur cluster. Defective FECH is the cause of porphyria.
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__TOC__
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== Function ==
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'''Bacterial ferrochelatase turns human: Tyr13 determines the apparent metal specificity of ''Bacillus subtilis'' ferrochelatase <ref>DOI 10.1007/s00775-010-0720-4</ref>'''
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'''Ferrochelatase''' (FECH) catalyzes the last step in the formation of heme. FECH adds Fe+2 to protoporphyrin IX converting it to protoheme. The human FECH is a homodimer containing 2 similar domains and an iron-sulfur cluster. '''Sirohydrochlorin ferrochelatase''' (SirB) catalyzes the addition of Fe+2 to sirohydrochlorin to produce siroheme.
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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/6'>metal ions is species specific</scene>. 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. <scene name='Journal:JBIC:4/Iron_binding_zoomout/4'>Our structural work</scene> 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 and ''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 <scene name='Journal:JBIC:4/Cobalt_bound_met_out/10'>we changed the Tyr to a Met residue</scene> and showed that the metal specificity changed so that the modified ''B. subtilis'' ferrochelatase <scene name='Journal:JBIC:4/Cobalt_bound_met/3'>preferred cobalt over copper</scene>. 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.
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== Disease ==
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</StructureSection>
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__NOTOC__
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==3D structures of ferrochelatase==
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Defective FECH is the cause of erythropoietic protoporphyria (EPP), an inherited disorder of heme synthesis <ref>PMID 11929052</ref>.
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
 
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[[1ak1]] – BsFECH – ''Bacillus subtilis''<br />
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'''Bacterial ferrochelatase turns human: Tyr13 determines the apparent metal specificity of ''Bacillus subtilis'' ferrochelatase <ref>DOI 10.1007/s00775-010-0720-4</ref>'''
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[[2ac4]] - BsFECH (mutant) <br />
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[[1doz]] - BsFECH + Mg<br />
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[[1ld3]] - BsFECH + Zn<br />
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[[2ac2]] - BsFECH (mutant) + Zn<br />
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[[2h1v]], [[3goq]] - BsFECH (mutant) + Mg<br />
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[[2h1w]] - BsFECH (mutant) + Fe + Mg<br />
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[[2hk6]] - BsFECH + Fe+ Mg<br />
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[[1n0i]] - BsFECH + Cd + Mg<br />
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[[3m4z]] - BsFECH + Co + Mg<br />
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[[1l8x]] - yFECH + Co – yeast<br />
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[[1lbq]] - yFECH<br />
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[[2qd4]] - hFECH + Fe2S2 - human<br />
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[[1hrk]], [[2pnj]], [[2po5]], [[2po7]], [[3aqi]], [[4f4d]] - hFECH (mutant) + Fe2S2<BR />
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===Ferrochelatase complex with porphyrin===
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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/6'>metal ions is species specific</scene>. 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. <scene name='Journal:JBIC:4/Iron_binding_zoomout/4'>Our structural work</scene> 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 and ''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 <scene name='Journal:JBIC:4/Cobalt_bound_met_out/10'>we changed the Tyr to a Met residue</scene> and showed that the metal specificity changed so that the modified ''B. subtilis'' ferrochelatase <scene name='Journal:JBIC:4/Cobalt_bound_met/3'>preferred cobalt over copper</scene>. 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.
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[[2qd3]], [[3hcn]], [[3hco]], [[3hcp]] - hFECH + protoporphyrin IX + Fe2S2<BR />
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==3D structures of ferrochelatase==
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[[3hcr]] - hFECH + protoporphyrin IX + O2 + Fe2S2<BR />
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[[Ferrochelatase 3D structures]]
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[[2hre]], [[2qd1]], [[2qd2]] - hFECH (mutant) + protoporphyrin IX + Fe2S2<BR />
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[[2qd5]] - hFECH + protoporphyrin IX + Pb + Fe2S2<BR />
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</StructureSection>
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[[1c1h]] - BsFECH + N-methylmesoporphyrin + Mg<br />
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[[2q3j]], [[2q2o]] - BsFECH (mutant) + N-methylmesoporphyrin + Mg<br />
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[[2q2n]] – BsFECH + protoporphyrin IX + Mg<br />
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[[1c9e]] - BsFECH + N-methylmesoporphyrin + Cu + Mg<br />
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'''References'''
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== References ==
<references/>
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Ferrochelatase with methylmesoporphyrin and Mg+2 ion (PDB code 1c1h)

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References

  1. ↑ Chen FP, Risheg H, Liu Y, Bloomer J. Ferrochelatase gene mutations in erythropoietic protoporphyria: focus on liver disease. Cell Mol Biol (Noisy-le-grand). 2002 Feb;48(1):83-9. PMID:11929052
  2. ↑ 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

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

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