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| | ==prolyl hydroxylase in complex with hypoxia inducible factor oxygen degradation domain peptide fragment from Trichoplax adhaerens== | | ==prolyl hydroxylase in complex with hypoxia inducible factor oxygen degradation domain peptide fragment from Trichoplax adhaerens== |
| - | <StructureSection load='6f0w' size='340' side='right' caption='[[6f0w]], [[Resolution|resolution]] 1.30Å' scene=''> | + | <StructureSection load='6f0w' size='340' side='right'caption='[[6f0w]], [[Resolution|resolution]] 1.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6f0w]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Triad Triad]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6F0W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6F0W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6f0w]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trichoplax_adhaerens Trichoplax adhaerens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6F0W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6F0W FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</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]] 1.301Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6ye1|6ye1]]</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=6f0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f0w OCA], [https://pdbe.org/6f0w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6f0w RCSB], [https://www.ebi.ac.uk/pdbsum/6f0w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6f0w ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PHD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10228 TRIAD])</td></tr>
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| - | <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=6f0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f0w OCA], [http://pdbe.org/6f0w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6f0w RCSB], [http://www.ebi.ac.uk/pdbsum/6f0w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6f0w ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/I6QVT6_TRIAD I6QVT6_TRIAD] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Triad]] | + | [[Category: Large Structures]] |
| - | [[Category: Boleininger, A]] | + | [[Category: Trichoplax adhaerens]] |
| - | [[Category: McDonough, M A]] | + | [[Category: Boleininger A]] |
| - | [[Category: Schofield, C J]] | + | [[Category: McDonough MA]] |
| - | [[Category: Hypoxia inducible factor]] | + | [[Category: Schofield CJ]] |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Oxygen sensing]]
| + | |
| - | [[Category: Oxygenase]]
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| - | [[Category: Prolyl hydroxylase]]
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| Structural highlights
Function
I6QVT6_TRIAD
Publication Abstract from PubMed
Background: In humans and other animals, the chronic hypoxic response is mediated by hypoxia inducible transcription factors (HIFs) which regulate the expression of genes that counteract the effects of limiting oxygen. Prolyl hydroxylases (PHDs) act as hypoxia sensors for the HIF system in organisms ranging from humans to the simplest animal Trichoplax adhaerens. Methods: We report structural and biochemical studies on the T. adhaerens HIF prolyl hydroxylase (TaPHD) that inform about the evolution of hypoxia sensing in animals. Results: High resolution crystal structures (</=1.3 A) of TaPHD, with and without its HIFalpha substrate, reveal remarkable conservation of key active site elements between T. adhaerens and human PHDs, which also manifest in kinetic comparisons. Conclusion: Conserved structural features of TaPHD and human PHDs include those apparently enabling the slow binding/reaction of oxygen with the active site Fe(II), the formation of a stable 2-oxoglutarate complex, and a stereoelectronically promoted change in conformation of the hydroxylated proline-residue. Comparison of substrate selectivity between the human PHDs and TaPHD provides insights into the selectivity determinants of HIF binding by the PHDs, and into the evolution of the multiple HIFs and PHDs present in higher animals.
Born to sense: biophysical analyses of the oxygen sensing prolyl hydroxylase from the simplest animal Trichoplax adhaerens.,Lippl K, Boleininger A, McDonough MA, Abboud MI, Tarhonskaya H, Chowdhury R, Loenarz C, Schofield CJ Hypoxia (Auckl). 2018 Nov 9;6:57-71. doi: 10.2147/HP.S174655. eCollection 2018. PMID:30519597[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lippl K, Boleininger A, McDonough MA, Abboud MI, Tarhonskaya H, Chowdhury R, Loenarz C, Schofield CJ. Born to sense: biophysical analyses of the oxygen sensing prolyl hydroxylase from the simplest animal Trichoplax adhaerens. Hypoxia (Auckl). 2018 Nov 9;6:57-71. doi: 10.2147/HP.S174655. eCollection 2018. PMID:30519597 doi:http://dx.doi.org/10.2147/HP.S174655
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