View source for 2hre


==Structure of human ferrochelatase variant E343K with protoporphyrin IX bound==
<StructureSection load='2hre' size='340' side='right'caption='[[2hre]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2hre]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HRE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HRE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CHD:CHOLIC+ACID'>CHD</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=PP9:PROTOPORPHYRIN+IX'>PP9</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2hre FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hre OCA], [https://pdbe.org/2hre PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hre RCSB], [https://www.ebi.ac.uk/pdbsum/2hre PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hre ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/HEMH_HUMAN HEMH_HUMAN] Defects in FECH are the cause of erythropoietic protoporphyria (EPP) [MIM:[https://omim.org/entry/177000 177000]. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. EPP is a form of porphyria marked by excessive protoporphyrin in erythrocytes, plasma, liver and feces, and by widely varying photosensitive skin changes ranging from a burning or pruritic sensation to erythema, edema and wheals.<ref>PMID:1755842</ref> <ref>PMID:1376018</ref> <ref>PMID:7910885</ref> <ref>PMID:8757534</ref> <ref>PMID:9585598</ref> <ref>PMID:9740232</ref> <ref>PMID:10942404</ref> <ref>PMID:11375302</ref> <ref>PMID:12063482</ref> <ref>PMID:12601550</ref> <ref>PMID:15286165</ref> <ref>PMID:17196862</ref> 
== Function ==
[https://www.uniprot.org/uniprot/HEMH_HUMAN HEMH_HUMAN] Catalyzes the ferrous insertion into protoporphyrin IX.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hr/2hre_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2hre ConSurf].
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== Publication Abstract from PubMed ==
Ferrochelatase, the terminal enzyme in heme biosynthesis, catalyzes the insertion of ferrous iron into protoporphyrin IX to form protoheme IX. Human ferrochelatase is a homodimeric, inner mitochondrial membrane-associated enzyme that possesses an essential [2Fe-2S] cluster. In this work, we report the crystal structure of human ferrochelatase with the substrate protoporphyrin IX bound as well as a higher resolution structure of the R115L variant without bound substrate. The data presented reveal that the porphyrin substrate is bound deep within an enclosed pocket. When compared with the location of N-methylmesoporphyrin in the Bacillus subtilis ferrochelatase, the porphyrin is rotated by approximately 100 degrees and is buried an additional 4.5 A deeper within the active site. The propionate groups of the substrate do not protrude into solvent and are bound in a manner similar to what has been observed in uroporphyrinogen decarboxylase. Furthermore, in the substrate-bound form, the jaws of the active site mouth are closed so that the porphyrin substrate is completely engulfed in the pocket. These data provide insights that will aid in the determination of the mechanism for ferrochelatase.

Substrate interactions with human ferrochelatase.,Medlock A, Swartz L, Dailey TA, Dailey HA, Lanzilotta WN Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1789-93. Epub 2007 Jan 29. PMID:17261801<ref>PMID:17261801</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2hre" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ferrochelatase 3D structures|Ferrochelatase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Dailey HA]]
[[Category: Dailey TA]]
[[Category: Lanzilotta WN]]
[[Category: Medlock A]]
[[Category: Swartz L]]