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| | <StructureSection load='1s13' size='340' side='right'caption='[[1s13]], [[Resolution|resolution]] 2.29Å' scene=''> | | <StructureSection load='1s13' size='340' side='right'caption='[[1s13]], [[Resolution|resolution]] 2.29Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1s13]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S13 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1S13 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1s13]] 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=1S13 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1S13 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2FH:2-PHENYLHEME'>2FH</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.29Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HMOX1 or HO1 or HO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2FH:2-PHENYLHEME'>2FH</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></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=1s13 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s13 OCA], [https://pdbe.org/1s13 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1s13 RCSB], [https://www.ebi.ac.uk/pdbsum/1s13 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1s13 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1s13 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s13 OCA], [http://pdbe.org/1s13 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1s13 RCSB], [http://www.ebi.ac.uk/pdbsum/1s13 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1s13 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN]] Defects in HMOX1 are the cause of heme oxygenase 1 deficiency (HMOX1D) [MIM:[http://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> | + | [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 == | | == Function == |
| - | [[http://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. | + | [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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Heme oxygenase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Buldain, G]] | + | [[Category: Buldain G]] |
| - | [[Category: Lad, L]] | + | [[Category: Lad L]] |
| - | [[Category: Montellano, P R.Ortiz de]] | + | [[Category: Niemevz F]] |
| - | [[Category: Niemevz, F]] | + | [[Category: Ortiz de Montellano PR]] |
| - | [[Category: Poulos, T L]] | + | [[Category: Poulos TL]] |
| - | [[Category: Wang, J]] | + | [[Category: Wang J]] |
| - | [[Category: Heme degradation]]
| + | |
| - | [[Category: Heme oxygenase-1]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Disease
HMOX1_HUMAN Defects in HMOX1 are the cause of heme oxygenase 1 deficiency (HMOX1D) [MIM: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.[1]
Function
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
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Human heme oxygenase-1 (hHO-1) catalyzes the O2-dependent oxidation of heme to biliverdin, CO, and free iron. Previous work indicated that electrophilic addition of the terminal oxygen of the ferric hydroperoxo complex to the alpha-meso-carbon gives 5-hydroxyheme. Earlier efforts to block this reaction with a 5-methyl substituent failed, as the reaction still gave biliverdin IXalpha. Surprisingly, a 15-methyl substituent caused exclusive cleavage at the gamma-meso-rather than at the normal, unsubstituted alpha-meso-carbon. No CO was formed in these reactions, but the fragment cleaved from the porphyrin eluded identification. We report here that hHO-1 cleaves 5-phenylheme to biliverdin IXalpha and oxidizes 15-phenylheme at the alpha-meso position to give 10-phenylbiliverdin IXalpha. The fragment extruded in the oxidation of 5-phenylheme is benzoic acid, one oxygen of which comes from O2 and the other from water. The 2.29- and 2.11-A crystal structures of the hHO-1 complexes with 1- and 15-phenylheme, respectively, show clear electron density for both the 5- and 15-phenyl rings in both molecules of the asymmetric unit. The overall structure of 15-phenylheme-hHO-1 is similar to that of heme-hHO-1 except for small changes in distal residues 141-150 and in the proximal Lys18 and Lys22. In the 5-phenylheme-hHO-1 structure, the phenyl-substituted heme occupies the same position as heme in the heme-HO-1 complex but the 5-phenyl substituent disrupts the rigid hydrophobic wall of residues Met34, Phe214, and residues 26-42 near the alpha-meso carbon. The results provide independent support for an electrophilic oxidation mechanism and support a role for stereochemical control of the reaction regiospecificity.
Human heme oxygenase oxidation of 5- and 15-phenylhemes.,Wang J, Niemevz F, Lad L, Huang L, Alvarez DE, Buldain G, Poulos TL, de Montellano PR J Biol Chem. 2004 Oct 8;279(41):42593-604. Epub 2004 Aug 5. PMID:15297453[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yachie A, Niida Y, Wada T, Igarashi N, Kaneda H, Toma T, Ohta K, Kasahara Y, Koizumi S. Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. J Clin Invest. 1999 Jan;103(1):129-35. PMID:9884342 doi:10.1172/JCI4165
- ↑ Wang J, Niemevz F, Lad L, Huang L, Alvarez DE, Buldain G, Poulos TL, de Montellano PR. Human heme oxygenase oxidation of 5- and 15-phenylhemes. J Biol Chem. 2004 Oct 8;279(41):42593-604. Epub 2004 Aug 5. PMID:15297453 doi:10.1074/jbc.M406346200
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