Prolyl hydroxylase domain

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See also [[Hydroxylase]]
See also [[Hydroxylase]]
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'''Prolyl hydroxylase domain''' (PHD) proteins mediate oxygen-dependent degradation of Hypoxia-inducible factor (HIF) α subunit. They include PHD1, PHD2 and PHD3. The PHD is a Fe+2/oxogluterate (2OG)-dependent enzyme. [[3ouh]] is the crystallized structure of the enzyme PHD2, an [[oxidoreductase]] that is 237 amino acids long with a molecular weight of 27 kDa. [[3ouh]] is found in [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and is a homolog of [http://en.wikipedia.org/wiki/EGLN1 EGLN1] found in [http://en.wikipedia.org/wiki/Caenorhabditis_elegans C. elegans].
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'''Prolyl hydroxylase domain''' (PHD) or '''egl nine homolog 1''' (PHD2/EGLN1) proteins mediate oxygen-dependent degradation of Hypoxia-inducible factor (HIF) α subunit. They include PHD1, PHD2 and PHD3. The PHD is a Fe+2/oxogluterate (2OG)-dependent enzyme. [[3ouh]] is the crystallized structure of the enzyme PHD2, an [[oxidoreductase]] that is 237 amino acids long with a molecular weight of 27 kDa. [[3ouh]] is found in [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and is a homolog of [http://en.wikipedia.org/wiki/EGLN1 EGLN1] found in [http://en.wikipedia.org/wiki/Caenorhabditis_elegans C. elegans].
The protein has three ligands: <scene name='45/459221/Cv/4'>O14</scene> (a 1-(5-chloro-6-fluoro-1H-benzimidazol-2-yl)-1H-pyrazole-4-carboxylic acid), <scene name='45/459221/Cv/3'>Fe+2 (an iron ion)</scene>, and SO<sub>4</sub> (a sulfate ion). Water molecules are shown as red spheres. It is involved in mediating physiological responses to [http://en.wikipedia.org/wiki/Hypoxia_(medical) hypoxia] by degrading the transcription factor of a hypoxia-inducible factor HIF1-α. In hypoxic conditions, the activity of PHD2 lessens, causing an increase in HIF1-α, resulting in secretion of erythropoietin, anaerobic [[glycolysis]], and angiogenesis<ref>PMID:16686427</ref>.
The protein has three ligands: <scene name='45/459221/Cv/4'>O14</scene> (a 1-(5-chloro-6-fluoro-1H-benzimidazol-2-yl)-1H-pyrazole-4-carboxylic acid), <scene name='45/459221/Cv/3'>Fe+2 (an iron ion)</scene>, and SO<sub>4</sub> (a sulfate ion). Water molecules are shown as red spheres. It is involved in mediating physiological responses to [http://en.wikipedia.org/wiki/Hypoxia_(medical) hypoxia] by degrading the transcription factor of a hypoxia-inducible factor HIF1-α. In hypoxic conditions, the activity of PHD2 lessens, causing an increase in HIF1-α, resulting in secretion of erythropoietin, anaerobic [[glycolysis]], and angiogenesis<ref>PMID:16686427</ref>.
<ref>Rosen M D, Venkatesan H, Peltier H M, Bembenek S D, Kanelakis K C, Zhao L X, Leonard B E, Hocutt F M, Wu X, Palomino H L, Brondtetter T I, Haugh P V, Cagnon L, Yan W, Liotta L A, Young A, Mirzadegan T, Shankley N P, Barrett T D, Rabinowitz M H. Benzimidazole-2-pyrazole HIF Prolyl 4-Hydroxylase Inhibitors as Oral Erythropoietin Secretagogues. ACS Medicinal Chemical Letters. 2010 Oct 5.</ref> For more detalis see [[Molecular Playground/Prolyl Hydroxylase Domain (PHD) Enzyme]].
<ref>Rosen M D, Venkatesan H, Peltier H M, Bembenek S D, Kanelakis K C, Zhao L X, Leonard B E, Hocutt F M, Wu X, Palomino H L, Brondtetter T I, Haugh P V, Cagnon L, Yan W, Liotta L A, Young A, Mirzadegan T, Shankley N P, Barrett T D, Rabinowitz M H. Benzimidazole-2-pyrazole HIF Prolyl 4-Hydroxylase Inhibitors as Oral Erythropoietin Secretagogues. ACS Medicinal Chemical Letters. 2010 Oct 5.</ref> For more detalis see [[Molecular Playground/Prolyl Hydroxylase Domain (PHD) Enzyme]].
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</StructureSection>
</StructureSection>
== 3D Structures of prolyl hydroxylase domain ==
== 3D Structures of prolyl hydroxylase domain ==
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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{{#tree:id=OrganizedByTopic|openlevels=0|
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[[2y33]] – hPHD2 + Zn + quinolin derivative – human<br />
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*Prolyl hydroxylase domain containing Mn
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[[3ouh]], [[3oui]], [[5v18]] - hPHD2 + Fe + inhibitor<br />
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[[4kbz]] - hPHD2 (mutant) + Fe + inhibitor<br />
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**[[5l9r]] - hPHD2 catalytic domain residues 181-426 (mutant) + Mn + 2OG - human<br />
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[[5a3u]] - hPHD2 + Mn + inhibitor<br />
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**[[3hqr]], [[5l9b]] - hPHD2 catalytic domain (mutant) + Mn + HIF 1 α C terminal + 2OG<br />
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[[4jzr]] - hPHD2 + Ni + inhibitor<br />
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**[[5l9v]], [[5la9]], [[5las]] - hPHD2 catalytic domain (mutant) + Mn + HIF NODD domain + 2OG<br />
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[[3ouj]] - hPHD2 + Fe + 2OG<br />
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**[[4bqw]], [[4bqx]], [[4bqy]] - hPHD2 catalytic domain + Mn + quinolin derivative<br />
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[[5l9r]] - hPHD2 (mutant) + Mn + 2OG<br />
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**[[6st3]] - hPHD2 catalytic domain + Mn + pyrimidin derivative<br />
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[[3hqr]], [[5l9b]] - hPHD2 (mutant) + Mn + HIF 1 α C terminal + 2OG<br />
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**[[6yvt]] - hPHD2 catalytic domain + Mn + pyridin derivative<br />
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[[5l9v]], [[5la9]], [[5las]] - hPHD2 (mutant) + Mn + HIF NODD domain + 2OG<br />
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**[[6qgv]], [[5a3u]] - hPHD2 catalytic domain + Mn + inhibitor<br />
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[[3hqu]] - hPHD2 + Fe + HIF 1 α C terminal + quinolin derivative<br />
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**[[5ox6]], [[6ox5]] - hPHD2 catalytic domain + Mn + drug<br />
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[[2hbt]], [[2hbu]], [[2g19]], [[2g1m]], [[2y34]], [[4bqi]] - hPHD2 + Fe + quinolin derivative<br />
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**[[5lat]], [[5lb6]], [[5lbb]], [[5lbc]], [[5lbe]], [[5lbf]], [[4uwd]] - hPHD2 catalytic domain (mutant) + Mn + quinolin derivative<br />
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[[4bqw]], [[4bqx]], [[4bqy]] - hPHD2 + Mn + quinolin derivative<br />
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**[[4h6j]] – hPHD Pasb domain 238-348 (mutant) + aryl hydrocarbon nuclear translocator (mutant)<br />
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[[5lat]], [[5lb6]], [[5lbb]], [[5lbc]], [[5lbe]], [[5lbf]], [[4uwd]] - hPHD2 (mutant) + Mn + quinolin derivative<br />
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[[4h6j]] – hPHD Pasb domain (mutant) + aryl hydrocarbon nuclear translocator (mutant)<br />
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*Prolyl hydroxylase domain containing other metal ions
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[[5v1b]] - hPHD1 + Fe + inhibitor<br />
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**[[2y33]] – hPHD2 catalytic domain residues 181-426 + Zn + quinolin derivative – human<br />
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**[[3ouh]], [[3oui]], [[5v18]] - hPHD2 catalytic domain + Fe + inhibitor<br />
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**[[4kbz]] - hPHD2 catalytic domain (mutant) + Fe + inhibitor<br />
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**[[4jzr]] - hPHD2 catalytic domain + Ni + inhibitor<br />
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**[[3ouj]] - hPHD2 catalytic domain + Fe + 2OG<br />
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**[[3hqu]] - hPHD2 catalytic domain + Fe + HIF 1 α C terminal + quinolin derivative<br />
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**[[2hbt]], [[2hbu]], [[2g19]], [[2g1m]], [[2y34]], [[4bqi]] - hPHD2 catalytic domain + Fe + quinolin derivative<br />
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**[[5v18]] - hPHD2 catalytic domain + Fe + pyridin derivative<br />
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**[[5v1b]] - hPHD1 catalytic domain + Fe + inhibitor<br />
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**[[6nmq]] - hPHD2 catalytic domain + Fe + inhibitor<br />
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}}
==References==
==References==
<references/>
<references/>

Revision as of 09:05, 7 October 2020

Human PHD2 catalytic domain complex with Fe+2 ion (orange), inhibitor and sulfate, 3ouh

Drag the structure with the mouse to rotate

3D Structures of prolyl hydroxylase domain

Updated on 07-October-2020

References

  1. ↑ Stolze IP, Mole DR, Ratcliffe PJ. Regulation of HIF: prolyl hydroxylases. Novartis Found Symp. 2006;272:15-25; discussion 25-36. PMID:16686427
  2. ↑ Rosen M D, Venkatesan H, Peltier H M, Bembenek S D, Kanelakis K C, Zhao L X, Leonard B E, Hocutt F M, Wu X, Palomino H L, Brondtetter T I, Haugh P V, Cagnon L, Yan W, Liotta L A, Young A, Mirzadegan T, Shankley N P, Barrett T D, Rabinowitz M H. Benzimidazole-2-pyrazole HIF Prolyl 4-Hydroxylase Inhibitors as Oral Erythropoietin Secretagogues. ACS Medicinal Chemical Letters. 2010 Oct 5.


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