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Prolyl hydroxylase domain: Difference between revisions

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<StructureSection load='' size='400' side='right' scene='45/459221/Cv/1' caption='Human PHD2 catalytic domain complex with Fe+2 ion (orange), inhibitor and sulfate, [[3ouh]]' pspeed='8'>
<StructureSection load='' size='400' side='right' scene='45/459221/Cv/1' caption='Human PHD2 catalytic domain complex with Fe+2 ion (orange), inhibitor and sulfate, [[3ouh]]' pspeed='8'>


'''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].
See also [[Hydroxylase]]
The protein has three ligands: <scene name='45/459221/Cv/2'>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 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>.
 
'''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>.
<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]].


</StructureSection>
== 3D Structures of prolyl hydroxylase domain ==
== 3D Structures of prolyl hydroxylase domain ==


[[2y33]] – hPHD2 + Zn + quinolin derivative – human<br />
[[Polyl hydroxylase domain 3D structures]]
[[3ouh]], [[3oui]], [[5v18]] - hPHD2 + Fe + inhibitor<br />
 
[[4kbz]] - hPHD2 (mutant) + Fe + inhibitor<br />
[[5a3u]] - hPHD2 + Mn + inhibitor<br />
[[4jzr]] - hPHD2 + Ni + inhibitor<br />
[[3ouj]] - hPHD2 + Fe + 2OG<br />
[[5l9r]] - hPHD2 (mutant) + Mn + 2OG<br />
[[3hqr]], [[5l9b]] - hPHD2 (mutant) + Mn + HIF 1 α C terminal + 2OG<br />
[[5l9v]], [[5la9]], [[5las]] - hPHD2 (mutant) + Mn + HIF NODD domain + 2OG<br />
[[3hqu]] - hPHD2 + Fe + HIF 1 α C terminal + quinolin derivative<br />
[[2hbt]], [[2hbu]], [[2g19]], [[2g1m]], [[2y34], [[4bqi]]], [[2y34]] - hPHD2 + Fe + quinolin derivative<br />
[[4bqw]], [[4bqx]], [[4bqy]] - hPHD2 + Mn + quinolin derivative<br />
[[5lat]], [[5lb6]], [[5lbb]], [[5lbc]], [[5lbe]], [[5lbf]], [[4uwd]] - hPHD2 (mutant) + Mn + quinolin derivative<br />
[[4h6j]] – hPHD Pasb domain (mutant) + aryl hydrocarbon nuclear translocator (mutant)<br />
[[5v1b]] - hPHD1 + Fe + inhibitor<br />
==References==
==References==
<references/>
<references/>
</StructureSection>
[[Category:Topic Page]]
[[Category:Topic Page]]
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Created with the participation of [[User:Andrew Winslow|Andrew Winslow]].
Created with the participation of [[User:Andrew Winslow|Andrew Winslow]].

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Michal Harel, Alexander Berchansky, Joel L. Sussman
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