1xk3: Difference between revisions

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-[[Image:1xk3.gif|left|200px]]<br />
-<applet load="1xk3" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1xk3, resolution 2.08&Aring;" />
-'''NADPH- and Ascorbate-Supported Heme Oxygenase Reactions are Distinct. Regiospecificity of Heme Cleavage by the R183E Mutant'''<br />
-==Overview==
+==NADPH- and Ascorbate-Supported Heme Oxygenase Reactions are Distinct. Regiospecificity of Heme Cleavage by the R183E Mutant==
-The ability of the human heme oxygenase-1 (hHO-1) R183E mutant to oxidize, heme in reactions supported by either NADPH-cytochrome P450 reductase or, ascorbic acid has been compared. The NADPH-dependent reaction, like that, of wild-type hHO-1, yields exclusively biliverdin IXalpha. In contrast, the R183E mutant with ascorbic acid as the reductant produces biliverdin, IXalpha (79 +/- 4%), IXdelta (19 +/- 3%), and a trace of IXbeta. In the, presence of superoxide dismutase and catalase, the yield of biliverdin, IXdelta is decreased to 8 +/- 1% with a corresponding increase in, biliverdin IXalpha. Spectroscopic analysis of the NADPH-dependent reaction, shows that the R183E ferric biliverdin complex accumulates, because, reduction of the iron, which is required for sequential iron and, biliverdin release, is impaired. Reversal of the charge at position 183, makes reduction of the iron more difficult. The crystal structure of the, R183E mutant, determined in the ferric and ferrous-NO bound forms, shows, that the heme primarily adopts the same orientation as in wild-type hHO-1., The structure of the Fe(II).NO complex suggests that an altered active, site hydrogen bonding network supports catalysis in the R183E mutant., Furthermore, Arg-183 contributes to the regiospecificity of the wild-type, enzyme, but its contribution is not critical. The results indicate that, the ascorbate-dependent reaction is subject to a lower degree of, regiochemical control than the NADPH-dependent reaction. Ascorbate may be, able to reduce the R183E ferric and ferrous dioxygen complexes in active, site conformations that cannot be reduced by NADPH-cytochrome P450, reductase.
+<StructureSection load='1xk3' size='340' side='right'caption='[[1xk3]], [[Resolution|resolution]] 2.08&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1xk3]] 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=1XK3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XK3 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]] 2.08&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NO:NITRIC+OXIDE'>NO</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=1xk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xk3 OCA], [https://pdbe.org/1xk3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xk3 RCSB], [https://www.ebi.ac.uk/pdbsum/1xk3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xk3 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN] Defects in HMOX1 are the cause of heme oxygenase 1 deficiency (HMOX1D) [MIM:[https://omim.org/entry/614034 614034]. A disease characterized by impaired stress hematopoiesis, resulting in marked erythrocyte fragmentation and intravascular hemolysis, coagulation abnormalities, endothelial damage, and iron deposition in renal and hepatic tissues. Clinical features include persistent hemolytic anemia, asplenia, nephritis, generalized erythematous rash, growth retardation and hepatomegaly.<ref>PMID:9884342</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN] Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed.
+== 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/xk/1xk3_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=1xk3 ConSurf].
+<div style="clear:both"></div>
-==Disease==
+==See Also==
-Known diseases associated with this structure: Epiphyseal dysplasia, multiple, 5 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602109 602109]], Heme oxygenase-1 deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141250 141250]], Osteoarthritis, hand, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602109 602109]], Spondyloepimetaphyseal dysplasia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602109 602109]]
+*[[Heme oxygenase 3D structures|Heme oxygenase 3D structures]]
+== References ==
-==About this Structure==
+<references/>
-XK3 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 HEM and NO as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Heme_oxygenase Heme oxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.3 1.14.99.3] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1XK3 OCA].
+__TOC__
+</StructureSection>
-==Reference==
-Regiospecificity determinants of human heme oxygenase: differential NADPH- and ascorbate-dependent heme cleavage by the R183E mutant., Wang J, Lad L, Poulos TL, Ortiz de Montellano PR, J Biol Chem. 2005 Jan 28;280(4):2797-806. Epub 2004 Nov 3. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15525643 15525643]
-[[Category: Heme oxygenase]]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Lad, L.]]
+[[Category: Lad L]]
-[[Category: Poulos, T.L.]]
+[[Category: Ortiz de montellano PR]]
-[[Category: Wang, J.]]
+[[Category: Poulos TL]]
-[[Category: montellano, P.R.Ortiz.de.]]
+[[Category: Wang J]]
-[[Category: HEM]]
-[[Category: NO]]
-[[Category: heme]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:06:39 2007''