2pnj

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{{Seed}}
 
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[[Image:2pnj.png|left|200px]]
 
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==Crystal structure of human ferrochelatase mutant with Phe 337 replaced by Ala==
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The line below this paragraph, containing "STRUCTURE_2pnj", creates the "Structure Box" on the page.
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<StructureSection load='2pnj' size='340' side='right'caption='[[2pnj]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2pnj]] is a 2 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=2PNJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PNJ FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35&#8491;</td></tr>
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<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></td></tr>
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{{STRUCTURE_2pnj| PDB=2pnj | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2pnj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pnj OCA], [https://pdbe.org/2pnj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pnj RCSB], [https://www.ebi.ac.uk/pdbsum/2pnj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pnj ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[https://www.uniprot.org/uniprot/HEMH_HUMAN HEMH_HUMAN] Catalyzes the ferrous insertion into protoporphyrin IX.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pn/2pnj_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2pnj ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Ferrochelatase catalyzes the terminal step in heme biosynthesis, the insertion of ferrous iron into protoporphyrin to form protoheme IX. The crystal structures of human ferrochelatase both with and without the protoporphyrin substrate bound have been determined previously. The substrate-free enzyme has an open active site pocket, while in the substrate-bound enzyme, the active site pocket is closed around the porphyrin macrocycle and a number of active site residues have reoriented side chains. To understand how and why these structural changes occur, we have substituted three amino acid residues (H263, H341, and F337) whose side chains occupy different spatial positions in the substrate-free versus substrate-bound ferrochelatases. The catalytic and structural properties of ferrochelatases containing the amino acid substitutions H263C, H341C, and F337A were examined. It was found that in the H263C and H341C variants, but not the F337A variant enzymes, the side chains of N75, M76, R164, H263, F337, H341, and E343 are oriented in a fashion similar to what is found in ferrochelatase with the bound porphyrin substrate. However, all of the variant forms possess open active site pockets which are found in the structure of porphyrin-free ferrochelatase. Thus, while the interior walls of the active site pocket are remodeled in these variants, the exterior lips remain unaltered in position. One possible explanation for this collective reorganization of active site side chains is the presence of a hydrogen bond network among H263, H341, and E343. This network is disrupted in the variants by alteration of H263C or H341C. In the substrate-bound enzyme, the formation of a hydrogen bond between H263 and a pyrrole nitrogen results in disruption of the network. The possible role of this network in catalysis is discussed.
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===Crystal structure of human ferrochelatase mutant with Phe 337 replaced by Ala===
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Altered orientation of active site residues in variants of human ferrochelatase. Evidence for a hydrogen bond network involved in catalysis.,Dailey HA, Wu CK, Horanyi P, Medlock AE, Najahi-Missaoui W, Burden AE, Dailey TA, Rose J Biochemistry. 2007 Jul 10;46(27):7973-9. Epub 2007 Jun 14. PMID:17567154<ref>PMID:17567154</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2pnj" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_17567154}}, adds the Publication Abstract to the page
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*[[Ferrochelatase 3D structures|Ferrochelatase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 17567154 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_17567154}}
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__TOC__
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</StructureSection>
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==Disease==
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Known disease associated with this structure: Protoporphyria, erythropoietic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=177000 177000]], Protoporphyria, erythropoietic, recessive, with liver failure OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=177000 177000]]
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==About this Structure==
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2PNJ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PNJ OCA].
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==Reference==
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Altered orientation of active site residues in variants of human ferrochelatase. Evidence for a hydrogen bond network involved in catalysis., Dailey HA, Wu CK, Horanyi P, Medlock AE, Najahi-Missaoui W, Burden AE, Dailey TA, Rose J, Biochemistry. 2007 Jul 10;46(27):7973-9. Epub 2007 Jun 14. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17567154 17567154]
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The 2.0 A structure of human ferrochelatase, the terminal enzyme of heme biosynthesis., Wu CK, Dailey HA, Rose JP, Burden A, Sellers VM, Wang BC, Nat Struct Biol. 2001 Feb;8(2):156-60. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11175906 11175906]
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Human ferrochelatase: crystallization, characterization of the [2Fe-2S] cluster and determination that the enzyme is a homodimer., Burden AE, Wu C, Dailey TA, Busch JL, Dhawan IK, Rose JP, Wang B, Dailey HA, Biochim Biophys Acta. 1999 Nov 16;1435(1-2):191-7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10561552 10561552]
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[[Category: Ferrochelatase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Burden, A E.]]
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[[Category: Burden AE]]
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[[Category: Dailey, H A.]]
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[[Category: Dailey HA]]
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[[Category: Dailey, T A.]]
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[[Category: Dailey TA]]
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[[Category: Horanyi, P.]]
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[[Category: Horanyi P]]
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[[Category: Medlock, A E.]]
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[[Category: Medlock AE]]
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[[Category: Najahi-Missaoui, W.]]
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[[Category: Najahi-Missaoui W]]
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[[Category: Rose, J P.]]
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[[Category: Rose JP]]
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[[Category: Wu, C K.]]
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[[Category: Wu C-K]]
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[[Category: F337a mutant]]
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[[Category: Fe2s2 cluster]]
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[[Category: Ferrochelatase]]
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[[Category: Heme biosynthesis]]
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[[Category: Mature length]]
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[[Category: Proteolytically processed mitochondrial inner membrane protein]]
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[[Category: Protoheme ferro-lyase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 07:20:06 2008''
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Current revision

Crystal structure of human ferrochelatase mutant with Phe 337 replaced by Ala

PDB ID 2pnj

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