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| | ==Crystal structure of human Heme Oxygenase-2 in complex with Myristate== | | ==Crystal structure of human Heme Oxygenase-2 in complex with Myristate== |
| - | <StructureSection load='5uc9' size='340' side='right' caption='[[5uc9]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='5uc9' size='340' side='right'caption='[[5uc9]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5uc9]] is a 4 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=5UC9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UC9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5uc9]] is a 4 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=5UC9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UC9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</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]] 1.903Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5uc8|5uc8]], [[5uca|5uca]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HMOX2, HO2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5uc9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uc9 OCA], [https://pdbe.org/5uc9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uc9 RCSB], [https://www.ebi.ac.uk/pdbsum/5uc9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uc9 ProSAT]</span></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_(biliverdin-producing) Heme oxygenase (biliverdin-producing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.18 1.14.14.18] </span></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=5uc9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uc9 OCA], [http://pdbe.org/5uc9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uc9 RCSB], [http://www.ebi.ac.uk/pdbsum/5uc9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uc9 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HMOX2_HUMAN HMOX2_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. Heme oxygenase 2 could be implicated in the production of carbon monoxide in brain where it could act as a neurotransmitter. | + | [https://www.uniprot.org/uniprot/HMOX2_HUMAN HMOX2_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. Heme oxygenase 2 could be implicated in the production of carbon monoxide in brain where it could act as a neurotransmitter. |
| | <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 5uc9" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5uc9" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Heme oxygenase 3D structures|Heme oxygenase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Luo, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Tong, L]] | + | [[Category: Luo S]] |
| - | [[Category: Heme oxygenase]] | + | [[Category: Tong L]] |
| - | [[Category: Myristic acid]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
HMOX2_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. Heme oxygenase 2 could be implicated in the production of carbon monoxide in brain where it could act as a neurotransmitter.
Publication Abstract from PubMed
N-myristoylation is the covalent attachment of myristic acid to the N terminus of proteins in eukaryotic cells. The matrix domain (MA) of HIV-1 Gag protein is N-myristoylated and plays an important role in virus budding. In screening for host factors that interact with HIV-1 MA, we found that heme oxygenase (HO-2) specifically binds the myristate moiety of Gag. HO-2 was also found to bind TRAM, an adaptor protein for Toll-like receptor 4 (TLR4), and thereby impact both virus replication and cellular inflammatory responses. A crystal structure revealed that HO-2 binds myristate via a hydrophobic channel adjacent to the heme-binding pocket. Inhibiting HO-2 expression, or blocking myristate binding with a heme analog, led to marked increases in virus production. HO-2 deficiency caused hyperresponsive TRAM-dependent TLR4 signaling and hypersensitivity to the TLR4 ligand lipopolysaccharide. Thus, HO-2 is a cellular myristate-binding protein that negatively regulates both virus replication and host inflammatory responses.
Heme Oxygenase 2 Binds Myristate to Regulate Retrovirus Assembly and TLR4 Signaling.,Zhu Y, Luo S, Sabo Y, Wang C, Tong L, Goff SP Cell Host Microbe. 2017 Feb 8;21(2):220-230. doi: 10.1016/j.chom.2017.01.002., Epub 2017 Jan 26. PMID:28132836[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhu Y, Luo S, Sabo Y, Wang C, Tong L, Goff SP. Heme Oxygenase 2 Binds Myristate to Regulate Retrovirus Assembly and TLR4 Signaling. Cell Host Microbe. 2017 Feb 8;21(2):220-230. doi: 10.1016/j.chom.2017.01.002., Epub 2017 Jan 26. PMID:28132836 doi:http://dx.doi.org/10.1016/j.chom.2017.01.002
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