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| | ==Crystal structure of human heme oxygenase 1 H25R with biliverdin bound== | | ==Crystal structure of human heme oxygenase 1 H25R with biliverdin bound== |
| - | <StructureSection load='5btq' size='340' side='right' caption='[[5btq]], [[Resolution|resolution]] 2.08Å' scene=''> | + | <StructureSection load='5btq' size='340' side='right'caption='[[5btq]], [[Resolution|resolution]] 2.08Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5btq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BTQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BTQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5btq]] 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=5BTQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BTQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BLA:BILIVERDINE+IX+ALPHA'>BLA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.08Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BLA:BILIVERDINE+IX+ALPHA'>BLA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5btq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5btq OCA], [http://pdbe.org/5btq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5btq RCSB], [http://www.ebi.ac.uk/pdbsum/5btq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5btq ProSAT]</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=5btq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5btq OCA], [https://pdbe.org/5btq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5btq RCSB], [https://www.ebi.ac.uk/pdbsum/5btq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5btq 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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5btq" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5btq" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Heme oxygenase 3D structures|Heme oxygenase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Heme oxygenase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Caaveiro, J M.M]] | + | [[Category: Large Structures]] |
| - | [[Category: Morante, K]] | + | [[Category: Caaveiro JMM]] |
| - | [[Category: Sigala, P]] | + | [[Category: Morante K]] |
| - | [[Category: Tsumoto, K]]
| + | [[Category: Sigala P]] |
| - | [[Category: Biliverdin biosensor]] | + | [[Category: Tsumoto K]] |
| - | [[Category: Heme coordination]] | + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Proximal histidine]]
| + | |
| - | [[Category: Site-directed mutagenesis]]
| + | |
| 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.
Publication Abstract from PubMed
Heme oxygenase (HO) is a ubiquitous enzyme with key roles in inflammation, cell signaling, heme disposal, and iron acquisition. HO catalyzes the oxidative conversion of heme to biliverdin (BV) using a conserved histidine to coordinate the iron atom of bound heme. This His-heme interaction has been regarded as being essential for enzyme activity, because His-to-Ala mutants fail to convert heme to biliverdin in vitro. We probed a panel of proximal His mutants of cyanobacterial, human, and plant HO enzymes using a live-cell activity assay based on heterologous co-expression in Escherichia coli of each HO mutant and a fluorescent biliverdin biosensor. In contrast to in vitro studies with purified proteins, we observed that multiple HO mutants retained significant activity within the intracellular environment of bacteria. X-ray crystallographic structures of human HO1 H25R with bound heme and additional functional studies suggest that HO mutant activity inside these cells does not involve heme ligation by a proximal amino acid. Our study reveals unexpected plasticity in the active site binding interactions with heme that can support HO activity within cells, suggests important contributions by the surrounding active site environment to HO catalysis, and can guide efforts to understand the evolution and divergence of HO function.
In-Cell Enzymology To Probe His-Heme Ligation in Heme Oxygenase Catalysis.,Sigala PA, Morante K, Tsumoto K, Caaveiro JM, Goldberg DE Biochemistry. 2016 Aug 30;55(34):4836-49. doi: 10.1021/acs.biochem.6b00562. Epub , 2016 Aug 15. PMID:27490825[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
- ↑ Sigala PA, Morante K, Tsumoto K, Caaveiro JM, Goldberg DE. In-Cell Enzymology To Probe His-Heme Ligation in Heme Oxygenase Catalysis. Biochemistry. 2016 Aug 30;55(34):4836-49. doi: 10.1021/acs.biochem.6b00562. Epub , 2016 Aug 15. PMID:27490825 doi:http://dx.doi.org/10.1021/acs.biochem.6b00562
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