2po5: Difference between revisions

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-[[Image:2po5.jpg|left|200px]]<br /><applet load="2po5" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="2po5, resolution 2.20&Aring;" />
-'''Crystal structure of human ferrochelatase mutant with His 263 replaced by Cys'''<br />
-==Overview==
+==Crystal structure of human ferrochelatase mutant with His 263 replaced by Cys==
-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.
+<StructureSection load='2po5' size='340' side='right'caption='[[2po5]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2po5]] 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=2PO5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PO5 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=CHD:CHOLIC+ACID'>CHD</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</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=2po5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2po5 OCA], [https://pdbe.org/2po5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2po5 RCSB], [https://www.ebi.ac.uk/pdbsum/2po5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2po5 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/po/2po5_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=2po5 ConSurf].
+<div style="clear:both"></div>
-==About this Structure==
+==See Also==
-PO5 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 <scene name='pdbligand=FES:'>FES</scene> and <scene name='pdbligand=CHD:'>CHD</scene> 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://oca.weizmann.ac.il/oca-bin/ocashort?id=2PO5 OCA].
+*[[Ferrochelatase 3D structures|Ferrochelatase 3D structures]]
+== References ==
-==Reference==
+<references/>
-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://ispc.weizmann.ac.il//pmbin/getpm?pmid=17567154 17567154]
+__TOC__
-[[Category: Ferrochelatase]]
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Burden, A.]]
+[[Category: Burden A]]
-[[Category: Dailey, H.A.]]
+[[Category: Dailey HA]]
-[[Category: Dailey, T.A.]]
+[[Category: Dailey TA]]
-[[Category: Horanyi, P.]]
+[[Category: Horanyi P]]
-[[Category: Medlock, A.E.]]
+[[Category: Medlock AE]]
-[[Category: Najahi-Missaoui, A.E.W.]]
+[[Category: Najahi-Missaoui AEW]]
-[[Category: Rose, J.P.]]
+[[Category: Rose JP]]
-[[Category: Wu, C.K.]]
+[[Category: Wu C-K]]
-[[Category: CHD]]
-[[Category: FES]]
-[[Category: ferrochelatase; h263c; fe2s2 cluster; heme biosynthesis; protoheme; ferro-lyase; mature length; proteolytically processed mitochondrial inner membrane protein]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:20:48 2008''