2qd2: Difference between revisions

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-[[Image:2qd2.gif|left|200px]]<br />
-<applet load="2qd2" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="2qd2, resolution 2.20&Aring;" />
-'''F110A variant of human ferrochelatase with protoheme bound'''<br />
-==Overview==
+==F110A variant of human ferrochelatase with protoheme bound==
-Ferrochelatase (protoheme ferrolyase, EC 4.99.1.1) is the terminal enzyme, in heme biosynthesis and catalyzes the insertion of ferrous iron into, protoporphyrin IX to form protoheme IX (heme). Due to the many critical, roles of heme, synthesis of heme is required by the vast majority of, organisms. Despite significant investigation of both the microbial and, eukaryotic enzyme, details of metal chelation remain unidentified. Here we, present the first structure of the wild-type human enzyme, a, lead-inhibited intermediate of the wild-type enzyme with bound metallated, porphyrin macrocycle, the product bound form of the enzyme, and a higher, resolution model for the substrate-bound form of the E343K variant. These, data paint a picture of an enzyme that undergoes significant changes in, secondary structure during the catalytic cycle. The role that these, structural alterations play in overall catalysis and potential, protein-protein interactions with other proteins, as well as the possible, molecular basis for these changes, is discussed. The atomic details and, structural rearrangements presented herein significantly advance our, understanding of the substrate binding mode of ferrochelatase and reveal, new conformational changes in a structurally conserved pi-helix that is, predicted to have a central role in product release.
+<StructureSection load='2qd2' size='340' side='right'caption='[[2qd2]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2qd2]] 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=2QD2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QD2 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]] 2.2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BCT:BICARBONATE+ION'>BCT</scene>, <scene name='pdbligand=CHD:CHOLIC+ACID'>CHD</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</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=2qd2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qd2 OCA], [https://pdbe.org/2qd2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qd2 RCSB], [https://www.ebi.ac.uk/pdbsum/2qd2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qd2 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/qd/2qd2_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2qd2 ConSurf].
+<div style="clear:both"></div>
-==About this Structure==
+==See Also==
-QD2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with BCT, FES, IMD, CHD and HEM as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Ferrochelatase Ferrochelatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.99.1.1 4.99.1.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2QD2 OCA].
+*[[Ferrochelatase 3D structures|Ferrochelatase 3D structures]]
+== References ==
-==Reference==
+<references/>
-A pi-Helix Switch Selective for Porphyrin Deprotonation and Product Release in Human Ferrochelatase., Medlock AE, Dailey TA, Ross TA, Dailey HA, Lanzilotta WN, J Mol Biol. 2007 Nov 2;373(4):1006-16. Epub 2007 Aug 23. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17884090 17884090]
+__TOC__
-[[Category: Ferrochelatase]]
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Dailey, H.A.]]
+[[Category: Dailey HA]]
-[[Category: Dailey, T.A.]]
+[[Category: Dailey TA]]
-[[Category: Lanzilota, W.N.]]
+[[Category: Lanzilota WN]]
-[[Category: Medlock, A.E.]]
+[[Category: Medlock AE]]
-[[Category: Ross, T.A.]]
+[[Category: Ross TA]]
-[[Category: BCT]]
-[[Category: CHD]]
-[[Category: FES]]
-[[Category: HEM]]
-[[Category: IMD]]
-[[Category: biosynthetic protein]]
-[[Category: ferrochelatase]]
-[[Category: heme biosynthesis]]
-[[Category: heme synthesis]]
-[[Category: iron]]
-[[Category: lyase]]
-[[Category: porphyrin biosynthesis]]
-[[Category: protoporphyrin ix]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 23:32:16 2007''