Prolyl hydroxylase domain: Difference between revisions

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Michal Harel, Alexander Berchansky, Joel L. Sussman

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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].
-The protein has three ligands: <scene name='45/459221/Cv/2'>O14 (a 1-(5-chloro-6-fluoro-1H-benzimidazol-2-yl)-1H-pyrazole-4-carboxylic acid)</scene>, <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>.
+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>.
 <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]].